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1.
Mitochondrial DNA B Resour ; 9(3): 398-402, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545569

RESUMO

The humped rockcod, Gobionotothen gibberifrons, is an Antarctic fish of the genus Gobionotothen in the family Nototheniidae and order Perciformes. To date, little biological information has been recorded about the genus Gobionotothen. Here, we report the first complete mitogenome of the genus Gobionotothen. The mitochondrial genome of G. gibberifrons is 18,631 bp in length, comprising 13 protein-coding genes, 24 tRNA genes (trnP-UGG and trnT-UGU were duplicated), 2 rRNA genes, and non-coding control regions. The base composition was 53.74% for A + T and 46.26% for G + C. This new mitochondrial genome of G. gibberifrons provides basic information for further phylogenetic analysis, suggesting the necessity to exploit a variety of newly discovered mitogenome sequences to infer inconclusive evolutionary relationships in Antarctic fishes.

2.
J Microbiol Biotechnol ; 34(5): 1135-1145, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38533592

RESUMO

When cells are exposed to freezing temperatures, high concentrations of cryoprotective agents (CPA) prevent ice crystal formation, thus enhancing cell survival. However, high concentrations of CPAs can also cause cell toxicity. Exopolysaccharides (EPSs) from polar marine environments exhibit lower toxicity and display effects similar to traditional CPA. In this study, we sought to address these issues by i) selecting strains that produce EPS with novel cryoprotective activity, and ii) optimizing culture conditions for EPS production. Sixty-six bacteria producing mucous substances were isolated from the Ross Sea (Antarctic Ocean) using solid marine agar plates. Among them, Pseudoalteromonas sp. RosPo-2 was ultimately selected based on the rheological properties of the produced EPS (p-CY02). Cryoprotective activity experiments demonstrated that p-CY02 exhibited significantly cryoprotective activity at a concentration of 0.8% (w/v) on mammalian cells (HaCaT). This activity was further improved when combined with various concentrations of dimethyl sulfoxide (DMSO) compared to using DMSO alone. Moreover, the survival rate of HaCaT cells treated with 5% (v/v) DMSO and 0.8% (w/v) p-CY02 was measured at 87.9 ± 2.8% after freezing treatment. This suggests that p-CY02 may be developed as a more effective, less toxic, and novel non-permeating CPA. To enhance the production of EPS with cryoprotective activity, Response Surface Methodology (RSM) was implemented, resulting in a 1.64-fold increase in production of EPS with cryoprotective activity.


Assuntos
Sobrevivência Celular , Crioprotetores , Meios de Cultura , Polissacarídeos Bacterianos , Pseudoalteromonas , Pseudoalteromonas/metabolismo , Polissacarídeos Bacterianos/farmacologia , Polissacarídeos Bacterianos/biossíntese , Polissacarídeos Bacterianos/metabolismo , Crioprotetores/farmacologia , Crioprotetores/metabolismo , Meios de Cultura/química , Regiões Antárticas , Humanos , Sobrevivência Celular/efeitos dos fármacos , Dimetil Sulfóxido/farmacologia , Dimetil Sulfóxido/metabolismo , Células HaCaT , Linhagem Celular , Água do Mar/microbiologia
3.
J Antibiot (Tokyo) ; 77(4): 257-263, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38243062

RESUMO

Using mass spectrometry (MS)-guided isolation methods, a new thiodiketopiperazine derivative (1) and exserohilone (2) were isolated from an EtOAc-extract of Setosphaeria rostrata culture medium. The chemical structure of the new compound was elucidated by MS and NMR spectroscopy, and the absolute configurations were established by the quantum mechanical calculations of electronic circular dichroism. All isolated compounds were examined for their effects on reactive oxygen species (ROS) production, matrix metalloproteinase 1 (MMP-1) secretion, and procollagen type I α1 secretion in tumor necrosis factor (TNF)-α-induced human dermal fibroblasts. Compound 1 and exserohilone (2) exhibited the inhibition of TNF-α-induced ROS generation and MMP-1 secretion. Additionally, compound 1 and exserohilone (2) increased the procollagen type I α1 secretion. Compound 1 docked computationally into the active site of MMP-1 (-6.0 kcal/mol).


Assuntos
Ascomicetos , Metaloproteinase 1 da Matriz , Fator de Necrose Tumoral alfa , Humanos , Metaloproteinase 1 da Matriz/farmacologia , Espécies Reativas de Oxigênio , Fibroblastos
4.
Bioorg Chem ; 143: 107070, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38190796

RESUMO

Three new fusidane-type nortriterpenoids, simplifusinolide A, 24-epi simplifusinolide A, and simplifusidic acid L (1-3), were isolated from the EtOAc extract of the Arctic marine-derived fungus Simplicillium lamellicola culture medium, together with fusidic acid (4) and 16-O-deacetylfusicid acid (5). The structures of the isolated compounds were elucidated by NMR and MS analyses. The absolute configurations of compounds 1-3 were established by the quantum mechanical calculations of electronic circular dichroism and gauge-including atomic orbital NMR chemical shifts, followed by DP4 + analysis. Benign prostatic hyperplasia (BPH) is a major urological disorder in men worldwide. The anti-BPH potentials of the isolated compounds were evaluated using BPH-1 and WPMY-1 cells. Treatment with simplifusidic acid L (3) and fusidic acid (4) significantly downregulated the mRNA levels of the androgen receptor (AR) and its downstream effectors, inhibiting the proliferation of BPH-1 cells. Specifically, treatment with 24-epi simplifusinolide A (2) significantly suppressed the cell proliferation of both BPH-1 and DHT-stimulated WPMY-1 cells by inhibiting AR signaling. These results suggest the potential of 24-epi simplifusinolide A (2), simplifusidic acid L (3) and fusidic acid (4) as alternative agents for BPH treatment by targeting AR signaling.


Assuntos
Hypocreales , Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/tratamento farmacológico , Ácido Fusídico/farmacologia , Extratos Vegetais/farmacologia , Proliferação de Células
5.
Biomater Sci ; 11(21): 7146-7157, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37718649

RESUMO

Cryopreservation of human red blood cells (RBCs) is vital for regenerative medicine and organ transplantation, but current cryoprotectants (CPAs) like glycerol and hydroxyethyl starch (HES) have limitations. Glycerol requires post-thaw washing due to cell membrane penetration, while HES causes high viscosity. To address these issues, we explored exopolysaccharides (EPS) from Antarctic Pseudoalteromonas sp. strain CY01 as a non-penetrating CPA for RBC cryopreservation. The EPS, p-CY01, consisted mainly of repeating (1-4) glucose and (1-6) galactose linkages with a molecular mass of 1.1 × 107 Da. Through mild acid hydrolysis, we obtained low molecular weight p-CY01 (p-CY01 LM) with a molecular weight of 2.7 × 105 Da, offering reduced viscosity, improved solubility, and cryoprotective properties. Notably, combining low concentrations of penetrating CPAs (>1% glycerol and dimethyl sulfoxide) with 2.5% (w/v) p-CY01 LM demonstrated significant cryoprotective effects. These findings highlight the potential of p-CY01 LM as a highly effective CPA for human RBC cryopreservation, replacing HES and glycerol and enabling the long-term storage of biological materials.

6.
Mitochondrial DNA B Resour ; 8(11): 1196-1199, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38196755

RESUMO

The complete mitochondrial genome of Trematomus newnesi was sequenced using an Illumina platform. The 18,602 bp mitogenome contains 13 protein-coding genes, two rRNAs, and 23 tRNAs (tRNAMet is duplicated). The eight stop codons are TAA, TAG, CTT, GTA, AAT, ACT, AGG, and TTA. Two start codons ATG and GTG are present. The GC content is 44.4% and AT content is 55.6%. A phylogenetic tree was generated using 13 species from three families. The results showed that T. newnesi is closely related to Pagothenia borchgrevinki in Nototheniidae. This study provides fundamental data for further genetic evolutionary studies on T. newnesi.

7.
Molecules ; 27(14)2022 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-35889426

RESUMO

Total fatty-acid (FA) contents of different organs (stomach, liver, brain, and skin) of two Antarctic fish, marbled rockcod (Notothenia rossii) and mackerel icefish (Champsocephalus gunnari), were examined using gas chromatography-mass spectrometry (GC-MS). N. rossii possessed higher contents of total omega-3, where eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the most represented omega-3 FAs, were distributed throughout all parts of the fish. The highest level of EPA was observed in the skin and that of DHA was observed in the brain of N. rossii. C. gunnari showed organ peculiarity in that most of the omega-3 FAs were found in stomach and skin. Specifically, the highest levels of EPA and DHA were both observed in the stomach. Although N. rossii and C. gunnari both inhabit the Antarctic Southern Oceans, their characteristics in terms of the composition of fatty acids were shown to vary. The extracts were also evaluated for matrix metalloproteinase-1 (MMP-1)-inhibitory activities in UVB-induced human dermal fibroblasts, where extracts of the skin and liver of N. rossii showed the most significant inhibition upon MMP-1 production. These findings provide experimental evidence that the extracts of the Antarctic fish could be utilized as bioactive nutrients, particularly in the enhancement of skin health.


Assuntos
Ácidos Graxos Ômega-3 , Perciformes , Animais , Regiões Antárticas , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Ácidos Graxos , Peixes , Humanos , Metaloproteinase 1 da Matriz
8.
Molecules ; 26(21)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34770857

RESUMO

The pathogenesis of Alzheimer's disease (AD) is still unclear, and presently there is no cure for the disease that can be used for its treatment or to stop its progression. Here, we investigated the therapeutic potential of ramalin (isolated from the Antarctic lichen, Ramalina terebrata), which exhibits various physiological activities, in AD. Specifically, derivatives were synthesized based on the structure of ramalin, which has a strong antioxidant effect, BACE-1 inhibition activity, and anti-inflammatory effects. Therefore, ramalin and its derivatives exhibit activity against multiple targets associated with AD and can serve as potential therapeutic agents for the disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Glutamatos/uso terapêutico , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Antioxidantes/síntese química , Antioxidantes/química , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Ácido Aspártico Endopeptidases/metabolismo , Compostos de Bifenilo/antagonistas & inibidores , Glutamatos/síntese química , Glutamatos/química , Humanos , Estrutura Molecular , Picratos/antagonistas & inibidores
9.
Biomed Res Int ; 2021: 8812090, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33644231

RESUMO

Umbilicaria antarctica (UA) is a member of the family Umbilicariaceae. To the best of our knowledge, no studies on its anti-inflammatory effects have been reported yet. In the present study, we examined its ability to suppress inflammatory responses and the molecular mechanisms underlying these abilities using lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells and a zebrafish model of inflammation. We investigated the effects of UA on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated RAW 264.7 cells. To explore the anti-inflammatory mechanisms of UA, we measured the mRNA and protein expression of proinflammatory mediators in LPS-stimulated RAW 264.7 cells using quantitative RT-PCR and western blot analyses, respectively. UA significantly inhibited the production of NO, PGE2, interleukin- (IL-) 6, and tumor necrosis factor- (TNF-) α in the LPS-stimulated RAW 264.7 cells. It also suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor- (NF-) κB activation in LPS-stimulated RAW 264.7 cells and tail pin-cutting-induced zebrafish model. Collectively, these findings indicate that UA significantly inhibits LPS-stimulated inflammatory responses. These effects were considered to be strongly associated with the suppression of NF-κB activation. Overall, our results demonstrate that UA extract exerts strong anti-inflammatory activities in in vitro and in vivo models and suggest that UA may be an effective novel therapeutic agent for the treatment of inflammatory diseases.


Assuntos
Anti-Inflamatórios/farmacologia , Ascomicetos/química , Misturas Complexas/farmacologia , Líquens/química , Lipopolissacarídeos/toxicidade , Animais , Anti-Inflamatórios/química , Misturas Complexas/química , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Metanol/química , Camundongos , Células RAW 264.7 , Peixe-Zebra
10.
Fish Shellfish Immunol ; 107(Pt A): 301-308, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33068759

RESUMO

The aim of the present study was to determine the anti-inflammatory effect of an extracts isolated from the lichen. Amandinea sp. was collected from the Antarctic and extracted with methanol. The basic screening of the anti-inflammatory property of the extracts was done using the NO assay. The extracts showed very little cytotoxicity, and reduced NO production in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. Furthermore, the extracts inhibited LPS-induced release of pro-inflammatory cytokines such as interleukin-6 (IL-6), and tumor necrosis factor-α(TNF-α), and inflammatory mediators inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The extracts also reduced the cytosolic p-IκB-α level and the level of the nuclear factor p65. We examined the anti-inflammatory effects of the extracts using zebrafish in vivo. The extracts reduced the amount of reactive oxygen species (ROS) in LPS-induced zebrafish larvae and inhibited the mRNA expression of inflammatory cytokines and mediators in a tail-cutting induced model. These results are similar to those obtained in vitro with RAW 264.7 cells. Collectively, the data suggest that the extracts may contain one of more compounds with anti-inflammatory effects. Further studies are required to identify the candidate compound/s and to understand the mechanism of action of the extract.


Assuntos
Anti-Inflamatórios/farmacologia , Ascomicetos/química , Doenças dos Peixes/tratamento farmacológico , Inflamação/veterinária , Líquens/química , Peixe-Zebra/imunologia , Animais , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Camundongos , Células RAW 264.7
11.
Aquat Toxicol ; 227: 105614, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32932040

RESUMO

The DNA repair system has evolved from the common ancestor of all life forms and its function is highly conserved within eukaryotes. In this study, to reveal the role of DNA double-strand break repair (DSB) genes in response to benzo[α]pyrene (B[α]P), we first identified DSB genes in relation to homologous recombination and non-homologous end joining events in four Brachionus rotifer spp.: B. calyciflorus, B. koreanus, B. plicatilis, and B. rotundiformis. In all the Brachionus spp., 39 orthologous genes to human DSB repair genes were identified. Furthermore, three genes in B. koreanus, two genes in B. plicatilis, and one gene in B. calyciflorus and B. rotundiformis were present as duplicated genes, indicating that these genes were diversified over speciation in the genus Brachionus. Moreover, we compared DSB repair genes on the gene structures in four monogonont Brachionus rotifers and the bdelloid rotifer Adineta vaga, which possesses highly efficient DNA repair ability. The transcriptional responses of four monogonont Brachionus rotifers in response to B[α]P exposure showed how B[α]P exposure led to DSBs and subsequently recruited DNA DSB repair pathways in the rotifer B. koreanus. Taken together, this study provides a better understanding of the potential role of DSB repair genes in the monogonont rotifer Brachionus spp. in response to B[α]P.


Assuntos
Benzo(a)pireno/toxicidade , Rotíferos/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Benzo(a)pireno/metabolismo , DNA/metabolismo , Quebras de DNA de Cadeia Dupla , Genoma , Humanos
12.
Int J Med Sci ; 16(2): 189-197, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30745798

RESUMO

Inflammation triggered by the innate immune system is a strategy to protect organisms from the risk of environmental infection. However, it has recently become clear that inflammation can cause a variety of human diseases, including cancer. In this study, we investigated the effects of an ethanol extract of the Antarctic freshwater microalgae, Chloromonas reticulata (ETCH), on inflammation and carcinogenesis in RAW 264.7 macrophages and HCT116 human colon cancer cells, respectively. ETCH exhibited significant anti-inflammatory activity through the dose-dependent modulation of major inflammatory markers such as COX-2, IL-6, iNOS, TNF-α, and NO production. For example, ETCH reduced LPS-induced upregulation of COX-2, IL-6, iNOS, and TNF- alpha mRNA levels, leading to a significant decrease in the levels of LPS-stimulated NO and IL-6 as well as TNF-alpha products. In contract, ETCH exhibited dose-dependent cytotoxic activity against HCT116 cells, yielding a profound reduction in the proliferation of the cancer cells. Furthermore, ETCH induced G2 phase cell cycle arrest by transcriptionally regulating of genes involved in G2 / M transition including p21 (CDKN1A), cyclin B1 (CCNB1), and CDK1; CDKN1A mRNA levels were upregulated in response to ETCH, whereas CCNB1 and CDK1 were downregulated. This study reports for the first time anti-inflammatory and anti-cancer effects of, C. reticulata and provides new insights into the molecular mechanisms of the linkage between inflammation and cancer.


Assuntos
Produtos Biológicos/uso terapêutico , Inflamação/terapia , Microalgas , Neoplasias/prevenção & controle , Animais , Produtos Biológicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Lipopolissacarídeos , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7
13.
Nat Ecol Evol ; 3(3): 469-478, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30804520

RESUMO

Icefishes (suborder Notothenioidei; family Channichthyidae) are the only vertebrates that lack functional haemoglobin genes and red blood cells. Here, we report a high-quality genome assembly and linkage map for the Antarctic blackfin icefish Chaenocephalus aceratus, highlighting evolved genomic features for its unique physiology. Phylogenomic analysis revealed that Antarctic fish of the teleost suborder Notothenioidei, including icefishes, diverged from the stickleback lineage about 77 million years ago and subsequently evolved cold-adapted phenotypes as the Southern Ocean cooled to sub-zero temperatures. Our results show that genes involved in protection from ice damage, including genes encoding antifreeze glycoprotein and zona pellucida proteins, are highly expanded in the icefish genome. Furthermore, genes that encode enzymes that help to control cellular redox state, including members of the sod3 and nqo1 gene families, are expanded, probably as evolutionary adaptations to the relatively high concentration of oxygen dissolved in cold Antarctic waters. In contrast, some crucial regulators of circadian homeostasis (cry and per genes) are absent from the icefish genome, suggesting compromised control of biological rhythms in the polar light environment. The availability of the icefish genome sequence will accelerate our understanding of adaptation to extreme Antarctic environments.


Assuntos
Adaptação Biológica , Ambientes Extremos , Genoma , Perciformes/genética , Animais , Regiões Antárticas , Feminino , Sequenciamento Completo do Genoma
14.
Int J Med Sci ; 15(9): 929-936, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30008606

RESUMO

Inflammation mediated by the innate immune system is an organism's protective mechanism against infectious environmental risk factors. It is also a driver of the pathogeneses of various human diseases, including cancer development and progression. Microalgae are increasingly being focused on as sources of bioactive molecules with therapeutic potential against various diseases. Furthermore, the antioxidant, anti-inflammatory, and anticancer potentials of microalgae and their secondary metabolites have been widely reported. However, the underlying mechanisms remain to be elucidated. Therefore, in this study, we investigated the molecular mechanisms underlying the anti-inflammatory and anticancer activities of the ethanol extract of the Antarctic freshwater microalga Micractinium sp. (ETMI) by several in vitro assays using RAW 264.7 macrophages and HCT116 human colon cancer cells. ETMI exerted its anti-inflammatory activity by modulating the main inflammatory indicators such as cyclooxygenase (COX)-2, interleukin (IL)-6, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and nitric oxide (NO) in a dose-dependent manner. In addition, ETMI exerted cytotoxic activity against HCT116 cells in a dose-dependent manner, leading to significantly reduced cancer cell proliferation. Further, it induced cell cycle arrest in the G1 phase through the regulation of hallmark genes of the G1/S phase transition, including CDKN1A, and cyclin-dependent kinase 4 and 6 (CDK4 and CDK6, respectively). At the transcriptional level, the expression of CDKN1A gradually increased in response to ETMI treatment while that of CDK4 and CDK6 decreased. Taken together, our findings suggest that the anti-inflammatory and anticancer activities of the Antarctic freshwater microalga, Micractinium sp., and ETMI may provide a new clue for understanding the molecular link between inflammation and cancer and that ETMI may be a potential anticancer agent for targeted therapy of colorectal cancer.


Assuntos
Antineoplásicos/farmacologia , Inflamação/tratamento farmacológico , Microalgas/química , Extratos Vegetais/farmacologia , Regiões Antárticas , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Ciclo-Oxigenase 2 , Etanol , Água Doce , Humanos , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Óxido Nítrico , Óxido Nítrico Sintase Tipo II , Fator de Necrose Tumoral alfa
15.
J Nat Prod ; 81(6): 1460-1467, 2018 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-29878768

RESUMO

The first total syntheses of the natural products lobaric acid (1) and its derivatives isolated from the Antarctic lichen Stereocaulon alpinum are reported in this study. Lobarin (3), with a pseudodepsidone structure, was synthesized first in 11 steps by utilizing an Ullmann aryl ether coupling reaction, and lobaric acid was synthesized in an additional three steps by a seven-membered lactonization reaction. Various derivatives were also obtained from the prepared lobaric acid, and the synthetic compounds exhibited significant PTP1B inhibitory activities.


Assuntos
Ascomicetos/química , Lactonas/química , Líquens/química , Éteres Fenílicos/química , Salicilatos/química , Regiões Antárticas , Depsídeos/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores
16.
Molecules ; 23(3)2018 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-29538328

RESUMO

Lobaric acid and lobarstin, secondary metabolites derived from the antarctic lichen Stereocaulon alpnum, exert various biological activities, including antitumor, anti-proliferation, anti-inflammation, and antioxidant activities. However, the underlying mechanisms of these effects have not yet been elucidated in human cervix adenocarcinoma and human colon carcinoma. In the present study, we evaluated the anticancer effects of lobaric acid and lobarstin on human cervix adenocarcinoma HeLa cells and colon carcinoma HCT116 cells. We show that the proliferation of Hela and HCT116 cells treated with lobaric acid and lobarstin significantly decreased in a dose- and time-dependent manner. Using flow cytometry analysis, we observed that the treatment with these compounds resulted in significant apoptosis in both cell lines, following cell cycle perturbation and arrest in G2/M phase. Furthermore, using immunoblot analysis, we investigated the expression of cell cycle and apoptosis-related marker genes and found a significant downregulation of the apoptosis regulator B-cell lymphoma 2 (Bcl-2) and upregulation of the cleaved form of the poly (ADP-ribose) polymerase (PARP), a DNA repair and apoptosis regulator. These results suggest that lobaric acid and lobarstin could significantly inhibit cell proliferation through cell cycle arrest and induction of apoptosis via the mitochondrial apoptotic pathway in cervix adenocarcinoma and colon carcinoma cells. Taken together, our data suggests that lobaric acid and lobarstin might be novel agents for clinical treatment of cervix adenocarcinoma and colon carcinoma.


Assuntos
Antineoplásicos/farmacologia , Benzofuranos/farmacologia , Neoplasias do Colo/metabolismo , Hidroxibenzoatos/farmacologia , Lactonas/farmacologia , Líquens/química , Salicilatos/farmacologia , Neoplasias do Colo do Útero/metabolismo , Antineoplásicos/isolamento & purificação , Benzofuranos/química , Benzofuranos/isolamento & purificação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Depsídeos/química , Depsídeos/isolamento & purificação , Depsídeos/farmacologia , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Células HeLa , Humanos , Hidroxibenzoatos/química , Hidroxibenzoatos/isolamento & purificação , Lactonas/química , Lactonas/isolamento & purificação , Estrutura Molecular , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Salicilatos/química , Salicilatos/isolamento & purificação , Neoplasias do Colo do Útero/tratamento farmacológico
17.
J Exp Zool B Mol Dev Evol ; 330(2): 76-82, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29441720

RESUMO

We report the complete sequence analysis of the entire complement of eight typical homeobox (Hox) genes (Lab, Pb, Dfd, Scr, Antp, Ubx, Abd-A, and Abd-B) and two other genes (Hox3 and Ftz) in a 324.6-kb region in the water flea Daphnia magna. In the cluster of D. magna Hox genes, we found one long interspersed nuclear element (LINE)/R2-NeSL between Ubx and Abd-A that was not present in Daphnia pulex Hox genes. In basal expression of Hox genes at different developmental stages, biothorax complex genes (Ubx, Abd-A, and Abd-B) and some antennapedia complex genes (Lab, Scr, Antp) were moderately expressed, but the Hox3 gene was barely expressed. Three homeobox genes (Antp, Ubx, Abd-A) were highly expressed at 6-7 days after release from the brood chamber and/or in the adult stage. The structural array and transcribed orientation of Dm-Hox genes were identical to those of the sister species D. pulex (∼340 kb), indicating that the Hox gene structure in daphnids is highly conserved. However, Dm- and Dp-Hox3, -deformed (Dfd), and -fushi tarazu (Ftz) genes varied from orthologous genes in pancrustacean species.


Assuntos
Sequência Conservada , Daphnia/genética , Genes Homeobox/genética , Família Multigênica , Animais , Elementos de DNA Transponíveis , Regulação da Expressão Gênica no Desenvolvimento , Genoma , Especificidade da Espécie
18.
Aquat Toxicol ; 196: 35-42, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29328974

RESUMO

Because of its widespread use, the pharmaceutical acetaminophen (APAP) is frequently detected in aquatic environments. APAP can have serious physiological effects, such as reduced reproduction, low growth rates, and abnormal behavior, in aquatic organisms. However, the methods available for evaluation of the aquatic toxicity of APAP are of limited usefulness. The present study aimed to develop reliable and sensitive markers for evaluation of APAP toxicity using Daphnia as a model organism. We focused on N-acetyl-p-benzoquinoneimine (NAPQI) production from APAP via cytochrome P450 metabolism because NAPQI causes APAP toxicity. Daphnia magna were exposed to APAP (0, 50, or 100 mg/L for 12 h or 24 h), and the total metabolites were extracted and analyzed for NAPQI. Direct detection of NAPQI was difficult because of its high reactivity, and its peak was close to that for APAP. Therefore, we tried to identify molecular and biochemical indicators associated with NAPQI generation, elimination, and its interactions with macromolecules. We identified changes in CYP370A13 gene expression, glutathione depletion, inhibition of thioredoxin reductase activity, and production of reactive oxygen species as indicators of D. magna exposure to APAP. These indicators could be used to develop sensitive and accurate techniques to evaluate the environmental toxicity of APAP.


Assuntos
Acetaminofen/toxicidade , Sistema Enzimático do Citocromo P-450/metabolismo , Daphnia/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Acetaminofen/análise , Acetaminofen/metabolismo , Animais , Benzoquinonas/análise , Benzoquinonas/toxicidade , Cromatografia Líquida de Alta Pressão , Sistema Enzimático do Citocromo P-450/genética , Daphnia/metabolismo , Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Iminas/análise , Iminas/toxicidade , Inativação Metabólica , Masculino , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxina Dissulfeto Redutase/metabolismo
19.
BMC Complement Altern Med ; 17(1): 509, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29191192

RESUMO

BACKGROUND: Cancer is a leading cause of human death around the world and occurs through the highly complex coordination of multiple cellular pathways. Recent studies have revealed that microalgal extracts exhibit considerable pharmaceutical activities, including those against various cancer cells. Thus, microalgae are promising candidates as novel cancer therapeutic drugs. In this study, we evaluated the biological functions of the ethanolic extract of the Antarctic freshwater microalga, Bo tryidiopsidaceae sp., such as its antioxidant, anti-proliferative, apoptotic and anti-invasive properties. METHODS: To estimate antioxidant capacity of ethanol extract of Bo tryidiopsidaceae sp. (ETBO), free radical 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays were used. The anti-proliferative activity of ETBO was assessed in several cancer cell lines (A375, Hs578T and HeLa) and non-tumorigenic keratinocyte cells (HaCaT), using MTT assay. In addition, Annexin V binding was performed to detect ETBO-induced apoptotic cells, and the expression levels of apoptosis-regulating proteins, caspase-3, p53, and Bcl-2, were determined by western blot. Boyden chamber assays were used to determine anti-migratory and anti-invasive properties of ETBO. RESULTS: ETBO exhibited antioxidant activity and concentration-dependent anticancer activities, such as anti-proliferation and pro-apoptotic activities against cancer cells. Furthermore, the expression of the apoptosis-inducing proteins, p53 and caspase-3, significantly increased in response to ETBO, whereas the expression of the anti-apoptotic protein, Bcl-2, decreased. These data imply that ETBO induces apoptosis by caspase activation through the modulation of pro-apoptotic and anti-apoptotic gene, p53 and Bcl-2, respectively. In addition, ETBO significantly inhibited migration and invasion of cervical cancer cells in a concentration-dependent manner. CONCLUSION: In this study, ETBO exhibited considerable anticancer activities, such as inhibition of proliferation, invasion, and migration, as well as induction of apoptosis. These data suggest that ETBO is a promising therapeutic agent in cancer therapy and drug discovery.


Assuntos
Antineoplásicos/farmacologia , Microalgas/química , Extratos Vegetais/farmacologia , Estramenópilas/química , Regiões Antárticas , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Água Doce , Células HeLa , Humanos , Extratos Vegetais/química
20.
Ecotoxicol Environ Saf ; 145: 511-517, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28783601

RESUMO

Oil pollution has deleterious effects on marine ecosystems. However, the toxicity of crude oil towards Antarctic marine organisms has not been well studied. We compared the deleterious effects of water accommodated fractions (WAFs) of crude oil on reproduction, intracellular reactive oxygen species (ROS) levels, and antioxidant enzymatic activity in Antarctic (Tigriopus kingsejongensis) and temperate (Tigriopus japonicus) copepods. Reproductive rates of T. kingsejongensis and T. japonicus were significantly reduced (P < 0.05) in response to WAFs. Furthermore, T. kingsejongensis showed elevated levels of ROS and higher antioxidant enzyme (glutathione peroxidase [GPx]) activity than T. japonicus in response to WAFs. CYP genes from congeneric copepods were identified and annotated to better understand molecular detoxification mechanisms. We observed significant up-regulation (P < 0.05) of Tk-CYP3024A3 and Tj-CYP3024A2 in response to WAFs, suggesting that CYP genes may contribute to the detoxification mechanism in response to WAF exposure. These finding also suggest that WAFs may induce oxidative stress, leading to reproductive impairment in copepods. Furthermore, Tk-CYP3024A3 and Tj-CYP3024A2 genes can be considered as potential biomarkers of WAF toxicity in the congeneric copepods T. kingsejongensis and T. japonicus. This study will be helpful for enhancing our knowledge on the harmful effects of WAFs in Antarctic and temperate copepods and provides insight into the underlying molecular mechanisms.


Assuntos
Copépodes/efeitos dos fármacos , Monitoramento Ambiental/métodos , Petróleo/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Regiões Antárticas , Copépodes/genética , Copépodes/metabolismo , Glutationa Peroxidase/genética , Estresse Oxidativo/efeitos dos fármacos , Petróleo/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reprodução/efeitos dos fármacos , Testes de Toxicidade Aguda , Regulação para Cima , Poluentes Químicos da Água/metabolismo
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