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1.
ACS Omega ; 8(21): 18543-18553, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37273629

RESUMO

One of the most common diseases in women is breast cancer, which has the highest death globally. Surgery, chemotherapy, hormone treatments, and radiation are the current treatment options for breast cancer. However, these options have several adverse side effects. Recently, peptide-based drugs have gained attention as anticancer therapy. Studies report that peptides from biological toxins such as venom and virulent pathogenic molecules have potential therapeutic effects against multiple diseases, including cancers. This study reports on the in vitro anticancer effect of a short peptide, PS9, derived from a virulent protein, glycosyl hydrolase, of an aquatic fungus, Aphanomyces invadans. This peptide arrests MCF-7 proliferation by regulating intercellular reactive oxygen species (ROS) and apoptotic pathways. Based on the potential for the anticancer effect of PS9, from the in silico analysis, in vitro analyses using MCF-7 cells were executed. PS9 showed a dose-dependent activity; its IC50 value was 25.27-43.28 µM at 24 h. The acridine orange/ethidium bromide (AO/EtBr) staining, to establish the status of apoptosis in MCF-7 cells, showed morphologies for early and late apoptosis and necrotic cell death. The 2,7-dichlorodihydrofluorescein diacetate (DCFDA) staining and biochemical analyses showed a significant increase in reactive oxygen species (ROS). Besides, PS9 has been shown to regulate the caspase-mediated apoptotic pathway. PS9 is nontoxic, in vitro, and in vivo zebrafish larvae. Together, PS9 may have an anticancer effect in vitro.

2.
Tissue Cell ; 80: 102000, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36542946

RESUMO

BACKGROUND: Excess accumulation of lipids leads to obesity. Triterpenoids are a group of plant compounds which poses various biological activities. The biological activities of Nimbin analogs N5 and N7 were addressed in this study on inhibiting lipid aggregation and underlying the derivatives molecular mechanisms for a therapeutical approach. AIM: This study aims to evaluate the anti-adipogenic activity of semi-natural Nimbin analogs, N5 and N7, on zebrafish larvae induced with oxidative stress due to a high-fat diet (HFD) and adipogenesis using specific fluorescent stains. MATERIALS AND METHODS: Zebrafish at 4 days post fertilized (dpf) larvae were divided into groups for the HFD diet along with exposure to various concentrations of N5 and N7. HFD induced accumulation of neutral lipids and triglycerides (Oil Red O and Nile red staining, respectively) with weight gain, which generated intracellular ROS (DCFH-DA staining) and superoxide anion production (DHE staining) with depleted glutathione levels (NDA staining) were assayed. HFD exposure promoted the accumulation of inflammatory macrophages (Neutral red staining) and impaired glucose metabolism (2NBDG staining). The ability of N5 and N7 to reduce total regulating lipogenic specific genes C/EBP-α, SREBP-1 and FAS were evaluated using relative gene expression. KEY FINDINGS: The Nimbin analogues N5 and N7 suppressed adipogenesis, forming intracellular ROS and superoxide anion while simultaneously restoring glutathione levels. The analogues significantly lowered total TC and TG levels, prevented inflammatory macrophage build-up and boosted glucose absorption. Also, N5 and N7 down-regulate the lipogenic-specific genes. SIGNIFICANCE: Nimbin analogs N5 and N7 enhance lipolysis and inhibit adipogenesis in in-vivo zebrafish larvae model.


Assuntos
Dieta Hiperlipídica , Peixe-Zebra , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Hipolipemiantes/metabolismo , Hipolipemiantes/farmacologia , Larva , Superóxidos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Adipogenia/genética , Triglicerídeos/metabolismo , Triglicerídeos/farmacologia , Glutationa/metabolismo , Camundongos Endogâmicos C57BL
3.
J Biotechnol ; 342: 79-91, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34751134

RESUMO

GR15 is a short molecule or peptide composed of aliphatic amino acids and possesses to have antioxidant properties. The GR15, 1GGGAFSGKDPTKVDR15 was identified from the protein S-adenosylmethionine synthase (SAMe) expressed during the sulfur departed state of Arthrospira platensis (spirulina or cyanobacteria). The in-silico assessment and the structural features of GR15 showed its antioxidant potency. Real-time PCR analysis found the up-regulation of ApSAMe expression on day 15 against oxidative stress due to 10 mM H2O2 treatment in A. platensis (Ap). The antioxidant activity of GR15 was accessed by the cell-free antioxidant assays such as ABTS, SARS, HRAS and NO; the results showed dose-dependent antioxidant activity. The toxicity assay was performed in both in vitro and in vivo models, in which peptide does not exhibit any toxicity in MDCK cell and zebrafish embryos. The intercellular ROS reduction potential of GR15 peptide was also investigated in both in vitro and in vivo models including LDH assay, antioxidant enzymes (SOD and CAT), and fluorescent staining assay (DCFDA, Hochest and Acridine orange sting) was performed; the results showed that the GR15 peptide was effectively reduced the ROS level. Further, RT-PCR demonstrated that GR15 enhanced the antioxidant property and also up-regulated the antioxidant gene, thus reduced the ROS level in both in vitro and in vivo models. Based on the results obtained from this study, we propose that GR15 has the potential antioxidant ability; hence further research can be directed towards the therapeutic product or drug development against disease caused by oxidative stress.


Assuntos
Antioxidantes , Spirulina , Animais , Antioxidantes/farmacologia , Cães , Peróxido de Hidrogênio , Larva/metabolismo , Células Madin Darby de Rim Canino , Estresse Oxidativo , Peptídeos/metabolismo , S-Adenosilmetionina , Spirulina/metabolismo , Peixe-Zebra/metabolismo
4.
Eur J Pharmacol ; 912: 174531, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34710370

RESUMO

Endothelial cell activation through nuclear factor-kappa-B (NFkB) and mitogen-activated protein kinases leads to increased biosynthesis of pro-inflammatory mediators, cellular injury and vascular inflammation under lipopolysaccharide (LPS) exposure. Recent studies report that LPS up-regulated global methyltransferase activity. In this study, we observed that a combination treatment with metformin (MET) and cholecalciferol (VD) blocked the LPS-induced S-adenosylmethionine (SAM)-dependent methyltransferase (SDM) activity in Eahy926 cells. We found that LPS challenge (i) increased arginine methylation through up-regulated protein arginine methyltransferase-1 (PRMT1) mRNA, intracellular concentrations of asymmetric dimethylarginine (ADMA) and homocysteine (HCY); (ii) up-regulated cell senescence through mitigated sirtuin-1 (SIRT1) mRNA, nicotinamide adenine dinucleotide (NAD+) concentration, telomerase activity and total antioxidant capacity; and (iii) lead to endothelial dysfunction through compromised nitric oxide (NOx) production. However, these LPS-mediated cellular events in Eahy926 cells were restored by the synergistic effect of MET and VD. Taken together, this study identified that the dual compound effect inhibits LPS-induced protein arginine methylation, endothelial senescence and dysfunction through the components of epigenetic machinery, SIRT1 and PRMT1, which is a previously unidentified function of the test compounds. In silico results identified the presence of vitamin D response element (VDRE) sequence on PRMT1 suggesting that VDR could regulate PRMT1 gene expression. Further characterization of the cellular events associated with the dual compound challenge, using gene silencing approach or adenoviral constructs for SIRT1 and/or PRMT1 under inflammatory stress, could identify therapeutic strategies to address the endothelial consequences in vascular inflammation-mediated atherosclerosis.


Assuntos
Antioxidantes/farmacologia , Colecalciferol/farmacologia , Metformina/farmacologia , Substâncias Protetoras/farmacologia , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas Repressoras/metabolismo , Sirtuína 1/metabolismo , Arginina/análogos & derivados , Arginina/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Senescência Celular/efeitos dos fármacos , Endotélio/efeitos dos fármacos , Homocisteína/metabolismo , Humanos , Lipopolissacarídeos/toxicidade , Metilação/efeitos dos fármacos , NAD/metabolismo , Óxido Nítrico/metabolismo , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteína-Arginina N-Metiltransferases/química , Proteína-Arginina N-Metiltransferases/genética , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/química , Proteínas Repressoras/genética , S-Adenosilmetionina/metabolismo , Sirtuína 1/genética , Telomerase/metabolismo , Elemento de Resposta à Vitamina D
5.
Cell Biol Int ; 45(11): 2331-2346, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34314086

RESUMO

In this study, we have identified a novel peptide NV14 with antioxidative functions from serine O-acetyltransferase (SAT) of Artrospira platensis (Ap). The full sequence of ApSAT and its derived NV14 peptide "NVRIGAGSVVLRDV" (141-154) was characterized using bioinformatics tools. To address the transcriptional activity of ApSAT in response to induce generic oxidative stress, the spirulina culture was exposed to H2 O2 (10 mM). The ApSAT expression was studied using RT-PCR across various time points and it was found that the expression of the ApSAT was significantly upregulated on Day 15. The in vitro cytotoxicity assay against NV14 was performed in human dermal fibroblast cells and human blood leukocytes. Results showed that NV14 treatment was non-cytotoxic to the cells. Besides, in vivo treatment of NV14 in zebrafish larvae did not exhibit the signs of developmental toxicity. Further, the in vitro antioxidant assays enhanced the activity of the antioxidant enzymes, such as SOD and CAT, due to NV14 treatment; and also significantly reduced the MDA levels, while increasing the superoxide radical and H2 O2 scavenging activity. The expression of antioxidant enzyme genes glutathione peroxidase, γ-glutamyl cysteine synthase, and glutathione S-transferase were found to be upregulated in the NV14 peptide pretreated zebrafish larvae when induced with generic oxidative stress, H2 O2 . Overall, the study showed that NV14 peptide possessed potent antioxidant properties, which were demonstrated over both in vitro and in vivo assays. NV14 enhanced the expression of antioxidant enzyme genes at the molecular level, thereby modulating and reversing the cellular antioxidant balance disrupted due to the H2 O2 -induced oxidative stress.


Assuntos
Antioxidantes/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Serina O-Acetiltransferase/genética , Animais , Antioxidantes/metabolismo , Cianobactérias/genética , Cianobactérias/metabolismo , Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/genética , Peróxido de Hidrogênio/farmacologia , Larva/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peptídeos , Serina O-Acetiltransferase/metabolismo , Superóxido Dismutase/metabolismo , Peixe-Zebra/genética
6.
Int J Biol Macromol ; 166: 641-653, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33137391

RESUMO

The antioxidant role of sulfite reductase (SiR) derived from Arthrospira platensis (Ap) was identified through a short peptide, TL15. The study showed that the expression of ApSiR was highly expressed on day ten due to sulfur deprived stress in Ap culture. TL15 peptide exhibited strong antioxidant activity when evaluated using antioxidant assays in a concentration ranging from 7.8 and 125 µM. Further, the cytotoxicity of TL15 peptide was investigated, even at the higher concentration (250 µM), TL15 did not exhibit any toxicity, when tested in vitro using human leucocytes. Moreover, a potential reduction in reactive oxygen species (ROS) production was observed due to the treatment of TL15 peptide (>15.6 µM) to H2O2 exposed leucocytes. For the in vivo assessment of TL15 toxicity and antioxidant ability, experiments were performed in zebrafish (Danio rerio) larvae to analyse the developmental toxicity of TL15 peptide. Results showed that, exposure to TL15 peptide in tested concentrations ranging from 10, 20, 40, and 80 µM, did not affect the development and physiological parameters of the zebrafish embryo/larvae such as morphology, survival, hatching and heart rate. Fluorescent assay was performed using DCFH-DA (2,7-dichlorodihydrofluorescein diacetate) to examine the production of intracellular reactive oxygen species (ROS) in zebrafish treated with TL15 peptide during the embryo-larval stages. Fluorescent images showed that pre-treatment with TL15 peptide to attenuate the H2O2 induced ROS levels in the zebrafish larvae in a dose-dependent manner. Further to uncover the underlying biochemical and antioxidant mechanism, the enzyme activity of superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPO) levels were studied in zebrafish larvae. TL15 pre-treated groups showed enhanced antioxidant enzyme activity, while the hydrogen peroxide (H2O2) exposed larvae showed significantly diminished activity. Overall results from the study revealed that, TL15 act as a potential antioxidant molecule with dose-specific antioxidant property. Thus, TL15 peptide could be an effective and promising source for biopharmaceutical applications.


Assuntos
Sequestradores de Radicais Livres/farmacologia , Radicais Livres/metabolismo , Oxidantes/toxicidade , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Peptídeos/farmacologia , Spirulina/enzimologia , Peixe-Zebra/metabolismo , Sequência de Aminoácidos , Animais , Antioxidantes/farmacologia , Benzotiazóis/química , Compostos de Bifenilo/química , Morte Celular/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Radical Hidroxila/química , Larva/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Modelos Animais , Peptídeos/química , Picratos/química , Ácidos Sulfônicos/química , Superóxidos/metabolismo , Peixe-Zebra/embriologia
7.
Eur J Pharmacol ; 891: 173697, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33144068

RESUMO

We investigated the role of protein arginine methylation (PAM) in estrogen receptor (ER)-positive breast cancer cells through pharmacological intervention. Tamoxifen (TAM) or adenosine dialdehyde (ADOX), independently, triggered cell cycle arrest and down-regulated PAM, as reduced protein arginine methyltransferase1 (PRMT1) mRNA and asymmetric dimethylarginine (ADMA) levels. Synergistic effect of these compounds elicited potent anti-cancer effect. However, reduction in ADMA was not proportionate with the compound-induced down-regulation of PRMT1 mRNA. We hypothesized that the disproportionate effect is due to the influence of the compounds on other methyltransferases, which catalyze the arginine dimethylation reaction and the diversity in the degree of drug-protein interaction among these methyltransferases. In silico analyses revealed that independently, ADOX or TAM, binds with phosphatidylethanolamine-methyltransferase (PEMT) or betaine homocysteine-methyl transferase (BHMT); and that the binding affinity of ADOX with PEMT or BHMT is prominent than TAM. These observations suggest that in breast cancer, synergistic effect of ADOX + TAM elicits impressive protective function by regulating PAM; and plausibly, restoration of normal enzyme activities of methyltransferases catalyzing arginine dimethylation could have clinical benefits.


Assuntos
Adenosina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas Repressoras/metabolismo , Tamoxifeno/farmacologia , Adenosina/metabolismo , Adenosina/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/metabolismo , Arginina/análogos & derivados , Arginina/metabolismo , Betaína-Homocisteína S-Metiltransferase/metabolismo , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Regulação para Baixo , Sinergismo Farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Metilação , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , Fosfatidiletanolamina N-Metiltransferase/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteínas Repressoras/genética , Transdução de Sinais , Tamoxifeno/metabolismo
8.
Dev Comp Immunol ; 114: 103863, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32918928

RESUMO

Antioxidant peptides are naturally present in food, especially in fishes, and are considered to contain rich source of various bioactive compounds that are structurally heterogeneous. This study aims to identify and characterize the antioxidant property of the WL15 peptide, derived from Cysteine and glycine-rich protein 2 (CSRP2) identified from the transcriptome of a freshwater food fish, Channa striatus. C. striatus is already studied to contain high levels of amino acids and fatty acids, besides traditionally known for its pharmacological benefits in the Southeast Asian region. In our study, in vitro analysis of WL15 peptide exhibited strong free radical scavenging activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), superoxide anion radical and hydrogen peroxide (H2O2) scavenging assay. Further, to evaluate the cytotoxicity and dose-response, the Human dermal fibroblast (HDF) cells were used. Results showed that the treatment of HDF cells with varying concentrations (10, 20, 30, 40 and 50 µM) of WL15 peptide was not cytotoxic. However, the treatment concentrations showed enhanced antioxidant properties by significantly inhibiting the levels of free radicals. For in vivo assessment, we have used zebrafish larvae for evaluating the developmental toxicity and for determining the antioxidant property of the WL15 peptide. Zebrafish embryos were treated with the WL15 peptide from 4 h of post-fertilization (hpf) to 96 hpf covering the embryo-larval developmental period. At the end of the exposure period, the larvae were exposed to H2O2 (1 mM) for inducing generic oxidative stress. The exposure of WL15 peptide during the embryo-larval period showed no developmental toxicity even in higher concentrations of the peptide. Besides, the WL15 peptide considerably decreased the intracellular reactive oxygen species (ROS) levels induced by H2O2 exposure. WL15 peptide also inhibited the H2O2-induced caspase 3-dependent apoptotic response in zebrafish larvae was observed using the whole-mount immunofluorescence staining. Overall results from our study showed that the pre-treatment of WL15 (50 µM) in the H2O2-exposed zebrafish larvae, attenuated the expression of activated caspase 3 expressions, reduced Malondialdehyde (MDA) levels, and enhanced antioxidant enzymes, including superoxide dismutase (SOD) and catalase (CAT). The gene expression of antioxidant enzymes such as glutathione S-transferase (GST), glutathione peroxide (GPx) and γ-glutamyl cysteine synthetase (GCS) was found to be upregulated. In conclusion, it can be conceived that pre-treatment with WL15 could mitigate H2O2-induced oxidative injury by elevating the activity and expression of antioxidant enzymes, thereby decreasing MDA levels and cellular apoptosis by enhancing the antioxidant response, demonstrated by the in vitro and in vivo experiments.


Assuntos
Derme , Fibroblastos , Sequestradores de Radicais Livres , Proteínas Musculares , Peptídeos , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Células Cultivadas , Derme/citologia , Embrião não Mamífero , Desenvolvimento Embrionário , Fibroblastos/imunologia , Sequestradores de Radicais Livres/metabolismo , Larva , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Estresse Oxidativo , Peptídeos/genética , Peptídeos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
9.
Bioresour Technol ; 323: 124561, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33373800

RESUMO

The magnetic graphene oxide (GO) supported with heterogeneous ternary mixed metal oxide (MMO) was used as nanocatalyst to enhance the conversion of waste frying oil (WFO) triglycerides to biodiesel via esterification process. In this regard, acidic MGO was modified with three basic metal cations of cerium, zirconium, and strontium oxides to produce heterogeneous MGO@MMO nanocatalyst. The nanocatalyst was characterized by FESEM, TEM, EDX and FTIR. The influence of different parameters such as catalyst material ratio, methanol to oil ratio, contact time, and reaction temperature was studied. Based on the results of effecting parameters, the MGO@MMO nanocatalyst converted WFO to biodiesel with a yield 94%, a reaction time of 90 min, methanol to oil ratio (8:1), and a temperature of 60 °C. Esterification mechanism indicated the MGO@MMO nanocatalyst having both binary Brønsted acid-base sites that increased the conversion yields as compared to MGO and MMO at low temperatures.


Assuntos
Biocombustíveis , Óxidos , Catálise , Esterificação , Grafite , Fenômenos Magnéticos , Óleos de Plantas
10.
Saudi J Biol Sci ; 27(11): 2980-2986, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33100856

RESUMO

This study was aimed to analyze the anti-cancer activity of silver nanoparticles (AgNPs) synthesized using aqueous plant extracts from the rhizome of Curcuma longa and Zingiber officinale. Synergistic aqueous extract of rhizome of C. longa and Z. officinale was used to green synthesis of AgNPs. Characterization of AgNPs was performed using UV-visible spectroscopy, FTIR, X-ray diffraction, TEM, and SEM analyses. Anti-cancer activity of AgNPs against human colon carcinoma (HT-29) cells was tested using MTT assay. UV-Visible spectroscopy analysis indicated the surface plasmon resonance (SPR) sharp peak at 350-430 nm wavelength that corresponds to the production of AgNPs. FTIR analysis reveals that existence of carboxyl (-C[bond, double bond]O) and amine (N-H) functional groups in the AgNPs. The X-ray diffraction analysis confirms four spectral peaks at 111, 200, 220, and 311. SEM analysis showed that AgNPs are in a spherical shape with a size of 42-61 nm and TEM analysis showed particle size are ranged between 20-51 nm. Anti-cancer study reveals that AgNPs had shown cytotoxicity against HT-29 cells at the concentrations ranged from 25 to 500 µg/mL and IC50 at 150.8 µg/mL. This study concludes that AgNPs synthesized using rhizome of Z. officinale and C. longa possesses potential anti-cancer activity.

11.
Int J Biol Macromol ; 165(Pt A): 1402-1409, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33045301

RESUMO

In this study, a well-organized, simplistic, and biological route of AgNPs (AgNPs) was synthesized using shrimp shell extracted chitin as reducing, capping and stabilizing factor under the optimized conditions. Also, the anticancer potential of synthesized biogenic AgNPs was evaluated against human hepatocarcinoma (HepG2) cells. Ultraviolet visible spectroscopy (UV-Vis spec) study indicated that the development of AgNPs present in the colloidal solution was single peak at 446 nm. FTIR results showed a strong chemical interaction between the chitin and biogenic AgNPs; whereas, XRD studies confirmed AgNPs presence in the composites. The SEM TEM analytical studies confirmed the synthesized AgNPs had a spherical shape crystalline structure with size ranges from 17 to 49 nm; EDX study also confirmed the percentage of weight and atomic elements available in the colloidal mixture. Furthermore, the synthesized AgNPs showed significant cytotoxic effect on the HepG2 cells with an IC50 value shown at 57 ± 1.5 µg/ml. The apoptotic and necrotic cell death effects of AgNPs were also confirmed by flow cytometry. The upregulated apoptotic related proteins Bax, cytochrome-c, caspase-3, caspase-9, PARP and downregulated anti-apoptotic related proteins Bcl-2 and Bcl-xl in cancer cells, confirmed the anticancer potential of AgNPs. These findings suggest that the AgNPs possess significant anticancer activity against HepG2 cells which could play major role in the therapeutic drug development to treat cancer in future.


Assuntos
Antineoplásicos/química , Carcinoma Hepatocelular/tratamento farmacológico , Quitina/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas Metálicas/química , Exoesqueleto/química , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 9/genética , Proliferação de Células/efeitos dos fármacos , Quitina/química , Crustáceos/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Prata/química
12.
Cell Biol Int ; 44(11): 2231-2242, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32716104

RESUMO

This study demonstrates both the antioxidant and anticancer potential of the novel short molecule YT12 derived from peroxiredoxin (Prx) of spirulina, Arthrospira platensis (Ap). ApPrx showed significant reduction in reactive oxygen species (ROS) against hydrogen peroxide (H2 O2 ) stress. The complementary DNA sequence of ApPrx contained 706 nucleotides and its coding region possessed 546 nucleotides between position 115 and 660. Real-time quantitative reverse transcription polymerase chain reaction analysis confirmed the messenger RNA expression of ApPrx due to H2 O2 exposure in spirulina cells at regular intervals, in which the highest expression was noticed on Day 20. Cytotoxicity assay was performed using human peripheral blood mononuclear cells, and revealed that at 10 µM, the YT12 did not exhibit any notable toxicity. Furthermore, ROS scavenging activity of YT12 was performed using DCF-DA assay, in which YT12 scavenged a significant amount of ROS at 25 µM in H2 O2 -treated blood leukocytes. The intracellular ROS in human colon adenocarcinoma cells (HT-29) was regulated by oxidative stress, where the YT12 scavenges ROS in HT-29 cells at 12.5 µM. Findings show that YT12 peptide has anticancer activity, when treated against HT-29 cells. Through the MTT assay, YT12 showed vital cytotoxicity against HT-29 cells. These finding suggested that YT12 is a potent antioxidant molecule which defends ROS against oxidative stress and plays a role in redox balance.


Assuntos
Peroxirredoxinas/metabolismo , Spirulina/metabolismo , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Humanos , Peróxido de Hidrogênio/metabolismo , Leucócitos Mononucleares/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Peptídeos/metabolismo , Peptídeos/farmacologia , Peroxirredoxinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Spirulina/genética
13.
J Photochem Photobiol B ; 210: 111966, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32711334

RESUMO

Cancer nanotheranostic materials are helpful in monitoring drug delivery and efficacy against tumor cells. Current chemotherapeutic may have adverse side effects and this necessity to discover the new modern therapeutic nano-drugs. In the present study, we designed the new targeted and degradable polymer of bio-active chitosan nanoparticles with proanthocyanidin (PAC-CSNPs) and evaluated its apoptotic effects against human colorectal carcinoma cells (HT-29). The functional groups were characterized by Fourier-transform infrared spectroscopy and transmission electron microscope. Further, their dispersion of spherical form nanoparticle with an average size of 73.43 nm used for drug delivery system. The PAC-CSNPs were targeted to inhibit the cyclin-dependent kinases and prevent cell cycle/cell division in cancer cells. At high concentrations of PAC (25 µg/mL) exposure, cell viability of HT-29 cells was greater than 80%. However, at low concentrations of PAC-CSNPs (6.25 µg/mL) exposure, HT-29 cell mortality was high, which may be due to the efficient drug release by CSNPs. The percentage of reactive oxygen species (ROS) levels were 12 ± 2.52% (control), 39 ± 4.32% (PAC), and 85.06 ± 3.54% (PAC-CSNPs). The over production of ROS by PAC-CSNPs can prompt DNA damage, cell death and apoptosis in HT-29 cells. The in vivo toxicity of synthesized PAC-CSNPs was tested against zebra fish observed at dose-time-dependent intervals. In conclusion, the PAC-CSNPs enhanced HT-29 cell death and shows promise as a novel future nano-therapy for cancer.


Assuntos
Quitosana/química , Nanopartículas/química , Proantocianidinas/química , Animais , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Portadores de Fármacos/química , Regulação da Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Nanopartículas/toxicidade , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Peixe-Zebra/crescimento & desenvolvimento
14.
Saudi J Biol Sci ; 27(4): 1107-1116, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32256172

RESUMO

The present context was investigated to purify and characterize anti-tubercular as well as anticancer protein from fermented food associated Staphylococcus hominis strain MANF2. Initially, the anti-tubercular potency of strain MANF2 was assessed against Mycobacterium tuberculosis H37Rv using luciferase reporter phase assay which revealed pronounced relative light unit (RLU) reduction of 92.5 ± 1.2%. The anticancer property of strain MANF2 was demonstrated against lung cancer (A549) and colon cancer (HT-29) cell lines using MTT assay which showed reduced viabilities. Anti-tubercular activities of the purified protein were observed to be increased significantly (P < 0.05) ranging from 34.6 ± 0.3 to 71.4 ± 0.4% of RLU reduction. Likewise, the purified protein showed significantly (P < 0.05) reduced viabilities of A549 and HT-29 cancer cells with IC50 values of 46.6 and 48.9 µg/mL, respectively. The nominal mass of the purified protein was found to be 7712.3 Da as obtained from MALDI-TOF MS/MS spectrum. The protein showed the sequence homology with 1-336 amino acids of Glyceraldehyde-3-phosphate dehydrogenase from Staphylococcus sp., thus, categorizing as a new class of Glyceraldehyde-3-phosphate dehydrogenase-like protein. The amino acid sequence of the most abundant peptide (m/z = 1922.12) in the purified protein was obtained as 'KAIGLVIPEIDGKLDGGAQRV' and it was identified as peptide NMANF2. In silico tools predicted significant stereo-chemical, physiochemical, and functional characteristics of peptide NMANF2. In a nutshell, protein purified from strain MANF2 can certainly be used as an ideal therapeutic agent against tuberculosis and cancer (lung and colon).

15.
J Photochem Photobiol B ; 206: 111868, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32259745

RESUMO

Yoghurt is a fermenting milk-based dairy product that has high nutritional benefits. It exhibits not only protection against osteoporosis but also enhances gut microbiota and aids digestion. In order to improve health beneficial aspects of yoghurt, this study was aimed to synthesize gold nanoparticles (AuNPs) using seeds oil of pomegranate (Punica granatum L.) and to formulate functional yoghurt for its antioxidant and anticancer properties. The synthesized AuNPs were characterized using UV-Vis spectrophotometer, FT-IR, XRD, EDX, SEM, DLS, and Zeta potential analyzer. The photo-induced synthesis of AuNPs showed particle size and zeta potential of 70 nm and +34 mV, respectively, with unique peak at 525 nm as observed using UV-Vis spectrophotometer. The FT-IR spectrum of AuNPs showed shifts in the functional groups from 3632.27 to 541.899 cm-1, thereby indicating the presence of various functional groups in pomegranate seed oil (PSO) and PSO-capped AuNPs. The AuNPs were observed to be smooth, elongated, and rectangular in shape. The PSO-capped AuNPs based formulation of functional yoghurt revealed DPPH degradation (23.6 ± 1.5 to 62.5 ± 1.8%) and H2O2 scavenging traits (21.6 ± 1.3 to 62.8 ± 1.8%) at varied concentrations. In addition, the PSO-capped AuNPs depicted strong anticancer attributes against lung and colon cancer with the cell viability ranging from 80.3 to 25% and 83.3 to 28.4.2%, respectively. Results concluded that the antioxidative components of PSO might have reduced and formulated AuNPs-based functional yoghurt. This functional yoghurt may reveal pivotal applications in food, nutraceuticals, and pharmaceuticals, especially as antioxidant and anticancer agents.

16.
J Infect Public Health ; 13(2): 235-243, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31585801

RESUMO

BACKGROUND: Unlike the terrestrial region, the microorganisms especially actinomycetes groups existing in the marine environment are important sources for the medically important drugs and other active compounds. Considering the importance of natural compounds from the marine actinomycetes, the present study proceeded to identify and characterize promising antibacterial and anticancer actinomycetes from the marine region of Saudi Arabia and to profile the individual chemical components. METHODS: Antimicrobial, anticancer and chemical profiling were performed by broth microdilution, mitochondrial membrane potential assays and GC-MS analysis. Investigations were directed towards the isolation and characterization of active Streptomyces sp. strain Al-Dhabi-97. RESULTS: The obtained results of the morphological, biochemical, physiological and molecular level studies of the isolate Al-Dhabi-97 showed similarity towards the species of Streptomyces. Gram positive bacteria such as Bacillus subtilis, Enterococcus faecalis, Staphylococcus epidermidis and Staphylococcus aureus showed MIC values of 500, 250, 125 and 62.5µg/ml and Gram negative bacteria such as Pseudomonas aeruginosa, Klebsiella pneumonia, Escherichia coli and Salmonella paratyphi reported MIC values of 500, 500, 250 and >250µg/ml in the antimicrobial studies. The results of anticancer studies showed that at 100µg/ml, the extract showed maximum cell growth inhibition and exhibited 2.5% necrosis, 62.2% late apoptosis and 20.8% early apoptosis in COLO 320 DM and VERO cell lines respectively. Chemical profiling of the extract authenticated the presence of constituents such as 1-phenanthrenemethanol (46.64%), phthalic acid, di(2-propylpentyl) ester (26.97%), benzenebutanoic acid (3.37%), podocarp-7-en-3-one (2.68%), and indole-3-carboxaldehyde (1.11%) respectively. CONCLUSION: The present study concluded that Saudi Arabian marine region was a promising area for the identification of medically important natural products producing actinomycetes for antibacterial and anticancer drugs.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Streptomyces/química , Actinobacteria , Animais , Antibacterianos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Organismos Aquáticos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Chlorocebus aethiops , Cromatografia Gasosa-Espectrometria de Massas , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Arábia Saudita , Água do Mar/microbiologia , Streptomyces/isolamento & purificação , Células Vero
17.
J Photochem Photobiol B ; 201: 111670, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31706087

RESUMO

Synthesis of nanoparticles using plant sources as reducing agent has become important, as physical and chemical methods are costlier and affects environment. Hence it is important to develop environment friendly nanoparticle synthesis by avoiding the use of toxic chemicals. The present study aimed to synthesize silver nanoparticles (Ag Nps) and gold nanoparticles (AuNps) using Musa acuminata colla flower and its pharmaceutical activity against extended spectrum beta-lactamase (ESBL) gene producing bacteria and anticancer efficacy. The synthesized Ag and Au NPs were analysed by means of UV-Vis, FTIR, XRD,SEM and EDAX evidenced the bioreduction of Ag+ ions to Ag0 and Au3+ ions to Au0 respectively. Both nanoparticles and flower extracts were studied for antibacterial activity of ESBL gene producing bacteria by disc diffusion and microdilution (Resazurin) method. In vitro anticancer efficacy (MCF-7) and toxicity (VERO) of AgNPs, AuNPs, aqueous extract and ethanol extract of flowers were performed by MTT assay. IC50 value for DPPH analysis was at 390 µg and 460 µg for ethanol and aqueous extract respectively. Total antioxidant content was found be 740 µg/mg and 460 µg/mg for ethanol and aqueous extract. GCMS analysis authenticated the existence of the compounds namely, 9,12-octadecadienoic acid(z,z)- and n-hexadecanoic acid in the crude extract of the samples. Among the samples, AgNPs had best antibacterial activity. AgNPs and AuNPs were confirmed by colour change to reddish brown and ruby red. Further ƛmax were obtained at 474 and 540 nm by UV - visible spectrum. SEM analysis revealed the particle size ranges from 12.6 to 15.7 nm for silver and 10.1 to 15.6 nm for gold nanoparticles. The EDAX spectrum shows a strong signal for elemental Ag and Au at ~ 3 keV and 1.5 keV. The XRD patterns for silver and gold nanoparticles at 36.701, 42.900, 63.281 and 76.398 corresponding to the lattice planes 2.4467, 2.1064, 1.46839, 1.24564 nm and 27.32, 36.7228, 39.56, 42.888, 63.253, 63.253, 65.02 and 76.383 corresponding to the lattice planes 3.262, 2.44530, 2.276, 2.1070, 1.46897, 1.4332 and 1.24585 nm. The IC50 values for MCF-7 and VERO cells were 30.0 µg/ml and 55.0 µg/ml respectively.


Assuntos
Antibacterianos/química , Antineoplásicos/química , Ouro/química , Musa/química , Prata/química , Animais , Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Flores/química , Flores/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Química Verde , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Musa/metabolismo , Extratos Vegetais/química , Células Vero
18.
Mater Sci Eng C Mater Biol Appl ; 102: 536-540, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31147025

RESUMO

ZnO nanoparticles with flakes-like structures were synthesized by simple wet chemical route using triethanolamine as a mild base. The well distributed ZnO nanoflakes onto carbon nanoplates (ZnO/C) were prepared by wet impregnation method. The crystalline structure and purity of the synthesized samples was inspected using XRD. The shape, structural morphology and elemental composition analysis was studied using FESEM and EDS. The probable anticancer activity of the synthesized samples was studied through their activity on human breast cancer MCF7 cell line. Exposure of breast cancer cells to ZnO and ZnO/C resulted in a dose dependent loss of cell viability, and the characteristic apoptotic features such as early and late apoptosis by dual staining. The results exhibited an enhanced antioxidant activity in the ZnO/C treated cells. This present study demonstrated that the ZnO and ZnO/C can be suggested as compounds with potential activity to induce apoptosis probable anticancer activity agents.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Carbono/química , Nanopartículas/química , Óxido de Zinco/química , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/química , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Humanos , L-Lactato Desidrogenase/metabolismo , Células MCF-7 , Nanopartículas/ultraestrutura , Picratos/química , Coloração e Rotulagem , Difração de Raios X
19.
J Photochem Photobiol B ; 191: 65-74, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30594044

RESUMO

Eco-friendly biosynthesis of nanoparticles from medicinal plants as reducing agent has gained importance due to its potential therapeutic uses. In the present study Silver nanoparticles (AgNPs) were eco-friendly synthesized using the leaf extracts of the medicinal plant Tropaeolum majus. The obtained AgNPs were characterized by UV - visible spectrum, FTIR, SEM and XRD which clearly showed the reduction of Ag+ ions to Ag0. In addition, the aqueous and ethanolic extracts were analyzed for phytochemicals and its antioxidant activities. GC-MS spectrum showed the presence of 25 compounds with benzeneacetic acid as the dominant contents. The synthesized AgNPs revealed maximum absorption spectrum at 463 nm and FTIR vibrational peaks at 3357.46, 21,966.52, 2118.42, 1637.27, 658.571 and 411.728 cm-1 respectively. SEM and XRD studies evidenced the nature of nanocrystalline with face centered cubic (fcc) crystal structure. Both AgNPs and plant extracts showed more inhibition activity against Pseudomonas aeroginosa compared to other bacteria with MIC value of 6.25 µg/ml. Antifungal activities was higher for Penicilium notatum with MIC value 31.2 µg/ml. The IC50 values for MCF7 for aqueous extract were found to be 4.68 µg/ml, ethanol extract 7.5 µg/ml, AgNPs 2.49 µg/ml, and doxorubicin 1.4 µg/ml. The IC50 values for VERO cell line for aqueous extract was 8.1 µg/ml, ethanol extract with 6.8 µg/ml, silver nanoparticles 5.3 µg/ml and doxorubicin 2.6 µg/ml respectively. Conclusively, the antibacterial, antifungal, antioxidant and anticancer properties of the synthesized AgNPs from Tropaeolum majus act as major therapeutic drug for microbial infectious disease and other health associated disorders.


Assuntos
Nanopartículas Metálicas/química , Extratos Vegetais/química , Tropaeolum/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Chlorocebus aethiops , Química Verde , Humanos , Células MCF-7 , Extratos Vegetais/farmacologia , Folhas de Planta/química , Prata/química , Células Vero
20.
J Photochem Photobiol B ; 190: 154-162, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30572187

RESUMO

The present study explored the one step extracellular green synthesis of Iron oxide (FexOy) and manganese oxide nanoparticles (MnNPs) using aqueous extract of Acorus calamus rhizome. The organic chemicals including polyphenol compounds responsible for bio-reduction and stabilization from the polyphenol enriched microwave irradiated aqueous extract of Acorus calamus were studied using GC-MS analysis. Further, their synthesis conditions were optimized using response surface methodology (RSM) and central composite design (CCD) using three variables. The green synthesized Iron oxide and Manganese oxide NPs were characterized by UV, FTIR, XRD, TEM and SEM. Results indicated that the Iron oxide NPs and mixture of iron and manganese NPs showed photocatalytic excellent activities in reducing dyes like methylene blue (0.1%) and Congo red (0.25%) at 0.03% NPs. However, Mn NPs showed moderate activity. On a contrary, manganese showed better larvicidal activity compared to Iron oxide NPs against the phytopathogens commonly affecting the vegetable crops. The present finding showed that high mortality rate at 30 µg/ml concentration of manganese NPs was comparatively interesting. In addition, NPs overall had appreciable activity with P. aeruginosa being more sensitive to Iron oxide NPs (22 ±â€¯2 mm zone of inhibition) and manganese NPs (13 ±â€¯2 mm zone of inhibition) and Iron oxide NPs completely inhibited the growth of A. flavus at 40 µg/ml concentration.


Assuntos
Acoraceae/química , Antibacterianos/síntese química , Compostos Azo/química , Química Verde/métodos , Inseticidas/síntese química , Aspergillus flavus/efeitos dos fármacos , Compostos Férricos/síntese química , Compostos de Manganês/síntese química , Nanopartículas/química , Nanopartículas/uso terapêutico , Óxidos/síntese química , Extratos Vegetais/química , Polifenóis/análise , Pseudomonas aeruginosa/efeitos dos fármacos
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