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1.
Int J Mol Sci ; 23(19)2022 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-36232636

RESUMEN

Estrogen receptors are indicators of breast cancer adaptability to endocrine therapies, such as tamoxifen. Deficiency or absence of estrogen receptor α (ER-α) in breast cancer cells results in reduced efficacy of endocrine therapy. Here, we investigated the effect of combined tamoxifen and pentadecanoic acid therapy on ER-α-under-expressing breast cancer cells. Drug resistance gene expression patterns were determined by RNA sequencing analysis and in vitro experiments. For the first time, we demonstrate that the combined treatment of pentadecanoic acid, an odd-chain fatty acid, and tamoxifen synergistically suppresses the growth of human breast carcinoma MCF-7 stem cells (MCF-7/SCs), which were found to be tamoxifen-resistant and showed reduced ER-α expression compared with the parental MCF-7 cells. In addition, the combined treatment synergistically induced apoptosis and accumulation of sub-G1 cells and suppressed epithelial-to-mesenchymal transition (EMT). Exposure to this combination induces re-expression of ER-α at the transcriptional and protein levels, along with suppression of critical survival signal pathways, such as ERK1/2, MAPK, EGFR, and mTOR. Collectively, decreased ER-α expression was restored by pentadecanoic acid treatment, resulting in reversal of tamoxifen resistance. Overall, pentadecanoic acid exhibits the potential to enhance the efficacy of endocrine therapy in the treatment of ER-α-under-expressing breast cancer cells.


Asunto(s)
Neoplasias de la Mama , Tamoxifeno , Antineoplásicos Hormonales/farmacología , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Receptores ErbB/metabolismo , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Ácidos Grasos/uso terapéutico , Femenino , Humanos , Células MCF-7 , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Serina-Treonina Quinasas TOR , Tamoxifeno/farmacología , Tamoxifeno/uso terapéutico
2.
Nutr Cancer ; 73(5): 845-855, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32482103

RESUMEN

Development of therapy resistance is a major clinical issue in breast cancer treatments. Breast cancer stem cells (bCSCs) have a clearly defined role in the development of breast cancer therapy resistance and tumor recurrence. Therefore, discovery of new treatment strategies to circumvent cancer therapy resistance and tumor recurrence by targeting bCSCs is desperately needed. Fruits of many Garcinia species are edible and, possess a range of health benefits. Garcinia quaesita, a species in the genus Garcinia, is endemic to Sri Lanka. Dried fruits of G. quaesita are commonly used to flavor dishes in Sri Lanka. The present study assessed the potential anticancer and apoptotic properties of G. quaesita fruit extracts in bCSCs using WST-1 cell proliferation assay, sphere formation assay, caspase 3/7 assay, real-time PCR and fluorescent and phase-contrast microscopy. DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and FRAP (Ferric Reducing Anti-oxidant Power) assays were used as anti-oxidant assays. The hexane extract of G. quaesita fruits was found to mediate cytotoxicity in bCSCs through induction of apoptosis. Furthermore, the hexane extract showed free radical scavenging ability. This pilot investigation provides a rationale to consume G. quaesita fruits as an anticancer dietary supplement for breast cancer patients.


Asunto(s)
Garcinia , Neoplasias de la Mama Triple Negativas , Apoptosis , Línea Celular , Frutas , Hexanos , Humanos , Células Madre Neoplásicas , Extractos Vegetales/farmacología
3.
Semin Cancer Biol ; 59: 147-160, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31128298

RESUMEN

Ovarian cancer (OC) is a lethal gynecological cancer. The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway plays an important role in the regulation of cell survival, growth, and proliferation. Irregularities in the major components of the PI3K/AKT/mTOR signaling pathway are common in human cancers. Despite the availability of strong pre-clinical and clinical data of PI3K/AKT/mTOR pathway inhibitors in OC, there is no FDA approved inhibitor available for the treatment of OC. Here, we outline the importance of PI3K/AKT/mTOR signaling pathway in OC tumorigenesis, proliferation and progression, and pre-clinical and clinical experience with several PI3K/AKT/mTOR pathway inhibitors in OC.


Asunto(s)
Neoplasias Ováricas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Epigénesis Genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Terapia Molecular Dirigida , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/etiología , Neoplasias Ováricas/patología , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Transducción de Señal/efectos de los fármacos
4.
Molecules ; 25(14)2020 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-32664351

RESUMEN

10-gingerol is a major phenolic lipid found in the rhizomes of ginger (Zingiber officinale). Being amphiphilic in nature, phenolic lipids have the ability to incorporate into cell membranes and modulate membrane properties. The purpose of the present study was to evaluate the effects of 10-gingerol on lipid raft/membrane raft modulation in radio-resistant triple negative breast cancer (MDA-MB-231/IR) cells. The effects of 10-gingerol on MDA-MB-231/IR cells' proliferation, clonogenic growth, migration, and invasion were assayed using MTT, colony formation, cell migration, and invasion assays, respectively. Sucrose density gradient centrifugation was used to extract lipid rafts. Western blotting and immunofluorescence were employed to assess the effects of 10-gingerol on lipid raft/membrane raft modulation and lipid rafts-associated PI3K/Akt signaling. Cholesterol measurements were carried out using a commercially available kit. 10-gingerol suppressed the proliferation, migration, invasion, and induced apoptosis through targeting the PI3K/Akt signaling pathway in MDA-MB-231/IR cells. Moreover, 10-gingerol was found to modulate the lipid rafts of MDA-MB-231/IR cells and attenuate the key PI3K/Akt signaling components in lipid rafts. The cholesterol content of the lipid rafts and rafts-resident Akt signaling were also affected by exposure to 10-gingerol. The results of the present study highlight rafts-associated PI3K/Akt signaling as a new target of 10-gingerol in MDA-MB-231/IR cells, thus rationalizing a new rafts-mediated treatment approach for radio-resistant triple negative breast cancer cells.


Asunto(s)
Catecoles/farmacología , Alcoholes Grasos/farmacología , Microdominios de Membrana/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Zingiber officinale/química , Humanos , Microdominios de Membrana/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo
5.
J Appl Toxicol ; 39(1): 38-71, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30073673

RESUMEN

Development of a cancer is a multistep process and six major hallmarks of cancer that are known to control malignant transformation have been described. Anticancer drug development is a tedious process, requiring a number of in vitro, in vivo and clinical studies. In vitro assays provide an initial platform for cancer drug discovery approaches. A wide range of in vitro assays/techniques have been developed to evaluate each hallmark feature of cancer and selection of a particular in vitro assay or technique mainly depends on the specific research question (s) to be examined. In the present review, we have described some commonly utilized in vitro assays and techniques used to examine cell viability/proliferation, apoptosis, cellular senescence, invasion and migration, oxidative stress and antioxidant effects, gene and protein expression, angiogenesis and genomic alterations in cancer drug discovery. Additionally, uses of modern techniques such as high throughput screening, high content screening and reporter gene assays in cancer drug discovery have also been described.


Asunto(s)
Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Descubrimiento de Drogas/métodos , Evaluación Preclínica de Medicamentos/métodos , Neoplasias/tratamiento farmacológico , Células Tumorales Cultivadas/efectos de los fármacos , Humanos
6.
Scientifica (Cairo) ; 2023: 6360487, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37885471

RESUMEN

Histone deacetylation is a key biochemical event associated with transcriptional regulation. Histone deacetylases (HDACs) mediate the deacetylation of histones. Fatty acids have been reported to function as histone deacetylase inhibitors (HDACi). The present instigation reports the HDAC inhibitory activity of egg yolks and egg yolk-derived fat of country and farm chicken for the first time. Egg yolks and fatty acids derived from both country (CCEF) and farm chicken (FCEF) demonstrated significant HDAC enzyme activity inhibition. Furthermore, egg yolks, CCEF, and FCEF exhibited DPPH free radical scavenging effects. The analysis of fatty acid profiles revealed varying degrees of saturated, mono-, and polyunsaturated fatty acids in the egg yolks. Palmitic acid (C16 : 0) was found to be the most abundant saturated fatty acid in both CCEF and FCEF. Among the monounsaturated fatty acids, oleic acid (C18 : 1) was the most abundant in both CCEF and FCEF. In terms of polyunsaturated fatty acids, a significant difference was observed in the content of linoleic acid (C18 : 2), an omega-6 fatty acid, and docosahexaenoic acid (C22 : 6), an omega-3 fatty acid, between CCEF and FCEF. These findings present exciting prospects for the development of histone deacetylase inhibitors based on egg yolk fat.

7.
Drug Discov Today ; 28(5): 103569, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36990144

RESUMEN

Histone acetylation is a key epigenetic event. Although the keywords fatty acids, histones, and histone acetylation have a long history in biochemistry, these topics continue to attract much attention among researchers. The acetylation of histones is controlled by the activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). An imbalance in the activities of HATs and HDACs is common in a range of human cancers. Histone deacetylase inhibitors (HDACi) can restore dysregulated histone acetylation profiles in cancer cells and have been identified as promising anti-cancer therapeutics. Short-chain fatty acids mediate anti-cancer effects by inhibiting the activity of HDACs. Recent studies have identified odd-chain fatty acids as novel HDACi. This review summarizes recent findings regarding fatty acids as HDACi in cancer therapy.


Asunto(s)
Disciplinas de las Ciencias Biológicas , Neoplasias , Humanos , Inhibidores de Histona Desacetilasas/farmacología , Histonas , Ácidos Grasos , Neoplasias/tratamiento farmacológico , Histona Desacetilasas/metabolismo , Histona Acetiltransferasas/metabolismo
8.
Nat Prod Res ; : 1-4, 2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38147311

RESUMEN

Goat milk is a rich source of fatty acids. This study intended to assess the inhibitory potential of goat milk and its extracted fatty acids on histone deacetylases (HDACs). Palmitic acid (C16:0) is the most prevalent saturated fatty acid in goat milk. Goat milk also contains a substantial amount of monounsaturated fatty acids, with oleic acid (C18:1) being the most abundant one. Additionally, the fatty acid profile of goat milk reveals the presence of polyunsaturated fatty acids, including linoleic acid (C18:2) and α-linolenic acid (C18:3n3). Interestingly, the fat extracted from goat milk showed a greater ability to inhibit HDAC enzymes in comparison to the whole milk. These findings, at least to the best of my knowledge, showed the HDAC inhibitory properties of goat milk for the first time, presenting new opportunities for the development of fatty acid-based epigenetic-targeted food products derived from goat milk.

9.
Metabolites ; 13(3)2023 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-36984785

RESUMEN

Cancer cells reprogram their metabolism to meet biosynthetic needs and to adapt to various microenvironments. Accelerated glycolysis offers proliferative benefits for malignant cells by generating glycolytic products that move into branched pathways to synthesize proteins, fatty acids, nucleotides, and lipids. Notably, reprogrammed glucose metabolism and its associated events support the hallmark features of cancer such as sustained cell proliferation, hijacked apoptosis, invasion, metastasis, and angiogenesis. Overproduced enzymes involved in the committed steps of glycolysis (hexokinase, phosphofructokinase-1, and pyruvate kinase) are promising pharmacological targets for cancer therapeutics. In this review, we summarize the role of reprogrammed glucose metabolism in cancer cells and how it can be manipulated for anti-cancer strategies.

10.
Nutrients ; 15(8)2023 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-37111207

RESUMEN

Phytochemicals are natural compounds found in food ingredients with a variety of health-promoting properties. Phytochemicals improve host health through their direct systematic absorption into the circulation and modulation of the gut microbiota. The gut microbiota increases the bioactivity of phytochemicals and is a symbiotic partner whose composition and/or diversity is altered by phytochemicals and affects host health. In this review, the interactions of phytochemicals with the gut microbiota and their impact on human diseases are reviewed. We describe the role of intestinal microbial metabolites, including short-chain fatty acids, amino acid derivatives, and vitamins, from a therapeutic perspective. Next, phytochemical metabolites produced by the gut microbiota and the therapeutic effect of some selected metabolites are reviewed. Many phytochemicals are degraded by enzymes unique to the gut microbiota and act as signaling molecules in antioxidant, anti-inflammatory, anticancer, and metabolic pathways. Phytochemicals can ameliorate diseases by altering the composition and/or diversity of the gut microbiota, and they increase the abundance of some gut microbiota that produce beneficial substances. We also discuss the importance of investigating the interactions between phytochemicals and gut microbiota in controlled human studies.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Humanos , Colon/metabolismo , Intestinos , Fitoquímicos/farmacología , Fitoquímicos/metabolismo
11.
Biochem Mol Biol Educ ; 51(5): 551-556, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37314055

RESUMEN

The COVID-19 pandemic caused several educational challenges. Conducting laboratory experiments was an uphill task during the pandemic. Here, we developed a low-cost and reliable home-based experimental setup to teach column and thin layer chromatography (TLC) using silica gel granules available at home. Powdered silica gel, prepared by grinding silica gel granules, was used as the stationary phase. Iso-propyl alcohol, purchased from a pharmacy, was diluted with water and used as the mobile phase. A food coloring was chromatographically separated using the designed column. Moreover, TLC plates were prepared using powdered silica gel and a drop of food coloring was separated on TLC plates using the same mobile phase. In the article, we show our experiences by providing methods used to implement this experimental setup. We assume that this experimental setup will be helpful for other universities, research institutes and schools to develop online laboratory curricula to demonstrate basic chromatography techniques required for subjects such as chemistry, biochemistry and biology.


Asunto(s)
COVID-19 , Colorantes de Alimentos , Humanos , Cromatografía en Capa Delgada/métodos , Pandemias , Gel de Sílice , COVID-19/epidemiología
12.
Drug Discov Today ; 27(11): 103347, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36087905

RESUMEN

Irregularities in cholesterol metabolism occur in a range of human cancers. Cholesterol precursors and derivatives support tumorigenesis and weaken immune responses. Intriguing preclinical and clinical findings demonstrate that cholesterol biosynthesis inhibition achieved by targeting major events and metabolites in cholesterol metabolism is an ideal anti-tumor strategy. Investigations addressing the effects of ß-hydroxy ß-methylglutaryl-CoA (HMG-CoA) reductase (HMGCR), 2,3-oxidosqualene cyclase (OSC), squalene synthase (SQS), liver X receptors (LXR), and cholesterol trafficking and esterification inhibition on cancer progression have shown encouraging results. Notably, manipulation of cholesterol metabolism strengthens the function of immune cells in the tumor microenvironment (TME). In this review, I discuss the role of cholesterol metabolism in cancer progression and the latest research related to cholesterol metabolism-based anti-cancer therapies and intend to bring this stylish biochemistry topic to the Sri Lankan research landscape.

13.
Food Sci Nutr ; 10(3): 740-750, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35311172

RESUMEN

Bananas, one of the most widely consumed fruits worldwide, are a rich source of valuable phytochemicals. In this study, the antioxidant and the anticancer potential of banana flesh was investigated. Of the four kinds of banana flesh extracts, the hexane extract (HE) had the highest total polyphenol content (2.54 ± 0.60 mg GAE/g) and total flavonoid content (1.69 ± 0.34 mg RE/g), followed by the chloroform fraction, total ethanol extract, and ethanol fraction. HE was found to exert a strong radical scavenging activity on 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonicacid) (ABTS•) free radicals. According to the IC50 values in various cancer cell lines, HE was found to possess the greatest cell growth inhibitory potential in human pancreatic cancer PANC-1 cells and human triple-negative breast cancer MDA-MB-231 cells. HE induced apoptosis in PANC-1 and MDA-MB-231 cells, as evidenced by the appearance of condensation of chromatin, proteolytic activation of caspase-3 and 7, and increase in the level of the cleaved form of poly (ADP-ribose) polymerase protein. Gas chromatography mass spectrometry (GC-MS) analysis of HE identified several anticancer compounds including palmitic acid, linoleic acid, oleic acid, campesterol, stigmasterol, and γ-sitosterol, supporting the anticancer potential of HE. Our investigation provides a rationale for the use of banana flesh to minimize the risk of cancer-like diseases.

14.
Pharmaceutics ; 14(5)2022 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-35631492

RESUMEN

Targeting cancer stem cell metabolism has emerged as a promising therapeutic strategy for cancer treatment. Breast cancer stem cells (BCSCs) exert distinct metabolism machinery, which plays a major role in radiation and multidrug resistance. Therefore, exploring the mechanisms involved in energy utilization of BCSCs could improve the effectiveness of therapeutic strategies aimed at their elimination. This study was conducted to clarify the glucose metabolism machinery and the function of nootkatone, a bioactive component of grapefruit, in regulating glucose metabolism and stemness characteristics in human breast carcinoma MCF-7 stem cells (MCF-7SCs). In vivo experiments, transcriptomic analysis, seahorse XF analysis, MTT assay, Western blotting, mammosphere formation, wound healing, invasion assay, flow cytometric analysis, reverse transcription-quantitative polymerase chain reaction, and in silico docking experiments were performed. MCF-7SCs showed a greater tumorigenic capacity and distinct gene profile with enrichment of the genes involved in stemness and glycolysis signaling pathways compared to parental MCF-7 cells, indicating that MCF-7SCs use glycolysis rather than oxidative phosphorylation (OXPHOS) for their energy supply. Nootkatone impaired glucose metabolism through AMPK activation and reduced the stemness characteristics of MCF-7SCs. In silico docking analysis demonstrated that nootkatone efficiently bound to the active site of AMPK. Therefore, this study indicates that regulation of glucose metabolism through AMPK activation could be an attractive target for BCSCs.

15.
Nat Prod Res ; 36(11): 2923-2926, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34058937

RESUMEN

This study was conducted to determine the anti-cancer activity of 3-O-α-L-arabinosyl oleanolic acid (3-O-L-AO), a triterpenoid saponin, isolated from the leaves of Schumacheria castaneifolia Vahl in breast cancer stem cells (bCSCs) grown in hypoxia. Anti-proliferative effects of 3-O-L-AO in bCSCs were determined using WST-1 assay. Real-time PCR was employed to evaluate the effects of 3-O-L-AO on apoptosis. Compound 3-O-L-AO exerted greater anti-proliferative effect in bCSCs grown under hypoxic conditions. Treatment of bCSCs with 3-O-L-AO resulted in a significant up-regulation of Bax and p53 and a significant down-regulation of survivin, HIF-1α and HIF-2α. Activation of caspase 3/7 activity and apoptosis-related morphological changes in bCSCs exposed to 3-O-L-AO further confirmed that 3-O-L-AO can induce apoptosis. Collectively, the results obtained indicated that 3-O-L-AO can be considered as a new anti-cancer agent to target chemo- and radio-therapy-resistant bCSCs.


Asunto(s)
Neoplasias de la Mama , Ácido Oleanólico , Saponinas , Triterpenos , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Femenino , Inhibidores de Crecimiento/farmacología , Humanos , Células Madre Neoplásicas , Ácido Oleanólico/farmacología , Saponinas/farmacología , Triterpenos/farmacología
16.
Nat Prod Res ; 36(24): 6389-6392, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35084278

RESUMEN

Gedunin is a secondary metabolite found in neem tree. Since the first discovery of this compound, its bio-active properties have been continuously evaluated. However, the low hydrophobicity of gedunin decreases its bioavailability and pharmacokinetic profile. In the present investigation, a new liposomal nanocarrier for co-delivery of gedunin and P-glycoprotein (P-gp) siRNA [siRNA coated liposomal gedunin (Lipo-Ged-siRNA)] was developed to improve the anti-proliferative activity of gedunin. Characteristics of prepared Lipo-Ged-siRNA demonstrated promising effects. Lipo-Ged-siRNA showed greater anti-proliferative effects (IC50-8.5 µg/mL) followed by pure gedunin (IC50- 40.2 µg/mL) in breast cancer stem cells (bCSCs). Immunofluorescence analysis demonstrated reduced expression of P-gp following exposure to Lipo-Ged-siRNA. Furthermore, Lipo-Ged-siRNA affected the expression of ABCB1, Cyclin D1, Bax, p53, and surviving genes in bCSCs.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Neoplasias de la Mama , Humanos , Femenino , ARN Interferente Pequeño , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Liposomas , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Células Madre Neoplásicas/metabolismo
17.
Biochimie ; 186: 147-156, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33965456

RESUMEN

The dysregulation of histone deacetylases (HDACs) is closely associated with tumorigenesis and has emerged as a promising target for anti-cancer drugs. Some odd-chain fatty acids are present in trace levels in human tissue. Despite limited health benefits, there is increasing experimental evidence of nutritional benefits of odd-chain fatty acids. This study examines the effects of five odd-chain fatty acids (valeric, heptanoic, nonanoic, undecanoic, and pentadecanoic acid) as novel HDAC6 inhibitors. Examination of these fatty acids on the proliferation and clonogenic ability in various cancer cell lines revealed that pentadecanoic and undecanoic acid can strongly inhibit cancer cell proliferation. Heptanoic and nonanoic acid showed moderate anti-proliferative effects, while valeric acid demonstrated weak anti-proliferative effects. HDAC6 inhibitory activities were in the order of pentadecanoic acid (C15:0) > undecanoic acid (C11:0) > nonanoic acid (C9:0) > heptanoic acid (C7:0) > valeric acid (C5:0), consistent with the anti-proliferative assay results. All of these fatty acids promoted the acetylation of α-tubulin in MCF-7 breast and A549 lung cancer cells dose-dependently. In-silico molecular docking analysis showed that increasing the aliphatic carbon chain length facilitates binding to HDAC6 residues, which might be important for the inhibitory potential of HDAC6. This study shows the potential utility of odd-chain fatty acids for epigenetic-based cancer therapy.


Asunto(s)
Antineoplásicos , Ácidos Grasos , Histona Desacetilasa 6 , Inhibidores de Histona Desacetilasas , Simulación del Acoplamiento Molecular , Proteínas de Neoplasias , Neoplasias , Células A549 , Antineoplásicos/química , Antineoplásicos/farmacología , Ácidos Grasos/química , Ácidos Grasos/farmacología , Células Hep G2 , Histona Desacetilasa 6/antagonistas & inhibidores , Histona Desacetilasa 6/química , Histona Desacetilasa 6/metabolismo , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Células MCF-7 , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/enzimología
18.
Antioxidants (Basel) ; 10(5)2021 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-33922092

RESUMEN

We investigated the effects of cooking (steaming and microwaving) and processing (freeze-drying and hot-air-drying) methods on the antioxidant activity of broccoli florets. 2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•), and alkyl• free radical scavenging assays were employed to assess anti-oxidant potentials. The cytoprotective effect against oxidative damage induced by H2O2 was studied using hepatocellular carcinoma (HepG2) cells. Anti-proliferative effects were assessed in MCF-7 and MDA-MB-231 breast cancer cells. L-sulforaphane in broccoli extracts was quantified using high-performance liquid chromatography (HPLC). Steam and microwave treatments caused increases in total polyphenol content (TPC), whereas the total flavonoid content (TFC) decreased following steam treatment. A slight increase in TFC was observed in the microwaved samples. Extracts of all broccoli samples showed almost identical radical scavenging and cytoprotective effects. HPLC demonstrated that steamed (3 min)-freeze-dried (F-S3) and microwaved (2 min)-freeze-dried (F-M2) samples exhibited elevated levels of L-sulforaphane. In addition, the F-S3 and F-M2 extracts displayed strong anti-proliferative effects in MCF-7 cells, which correlated with L-sulforaphane content. As we observed no significant decrease in the antioxidant activity of broccoli florets, the cooking and processing methods and conditions studied here are recommended for broccoli.

19.
Oncol Rep ; 45(3): 1133-1141, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33650657

RESUMEN

Overcoming chemo­ and radio­resistance is a major challenge in pancreatic cancer treatment. Therefore, there is an urgent need to discover novel therapeutic approaches to avoid chemo­ and radio­resistance in pancreatic cancer. Catechol is a phytochemical found in some fruits and vegetables. A few studies have reported on the potential anticancer effects of pure catechol. The present study aimed to explore the chemo­ and radio­sensitizing effects of catechol in Panc­1 human pancreatic cancer cells. The effects of catechol on Panc­1 cell proliferation, clonogenic survival, invasion, and migration were assessed using MTT, cell migration, and Transwell invasion assays. The chemo­ and radio­sensitizing effects of catechol on Panc­1 cells were evaluated via MTT assay and flow cytometry. Western blotting was conducted to analyze the expression of proteins involved in several mechanisms induced by catechol in Panc­1 cells, including growth inhibition, apoptosis, suppression of epithelial­mesenchymal transition (EMT), and chemo­ and radio­sensitizing activities. The results indicated that catechol inhibited proliferation, promoted apoptosis, and suppressed cell migration, invasion, and EMT in Panc­1 cells in a dose­dependent manner. Catechol treatment also induced the phosphorylation of AMP­activated protein kinase (AMPK) with a concomitant reduction in the expression of Hippo signaling pathway components, including Yes­associated protein, cysteine­rich angiogenic inducer 61, and connective tissue growth factor. In addition, catechol enhanced the chemosensitivity of Panc­1 cells to gemcitabine, a commonly used chemotherapy in pancreatic cancer treatment. A combination of catechol and radiation enhanced apoptosis and increased the expression of two radiation­induced DNA damage markers, p­ATM and p­Chk2. Collectively, the present results demonstrated that catechol, a naturally occurring compound, could suppress the proliferation of pancreatic cancer cells, reduce the expression of EMT­related proteins, and enhance the chemo­ and radio­sensitivity of Panc­1 cells by targeting AMPK/Hippo signaling.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Catecoles/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Pancreáticas/metabolismo , Tolerancia a Radiación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/radioterapia , Fosforilación , Factores de Transcripción/metabolismo , Proteínas Señalizadoras YAP , Gemcitabina
20.
ACS Appl Mater Interfaces ; 13(16): 18887-18896, 2021 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-33871964

RESUMEN

The biomolecules offer different metal-binding sites to form a coordination polymer with structural diversity. The coordination directed one-dimensional metal-biomolecule nanofibers (Cu-Asp NFs) designed using copper as metal ion and aspartate as a ligand for triboelectric nanogenerator (TENG) is reported here. The different characterization techniques reveal the detailed characteristics of the synthesized Cu-Asp NFs. The robust coating of the Cu-Asp NFs is achieved using a simple tape cast coater. The bending and water dipping studies suggest the stability of the coated material. The relative polarity test and Kelvin probe force microscopy (KPFM) reveal the position of Cu-Asp in the triboelectric series. The Cu-Asp NFs and Teflon are used as the active material for the fabrication of freestanding mode (NF-TENG) and contact-separation mode (cNF-TENG) TENG. The NF-TENG generates an output of 200 V and 6 µA. The simple ion deposition technique enhances the voltage, current, and transferred charge of cNF-TENG by 2.5, 8, and 3 times. The use of the material for the single electrode sliding mode device further confirms the coated material's stability and robustness. A selective self-powered thioacetamide sensor is developed with the cNF-TENG, which exhibits a sensitivity of 0.76 v mM-1. Finally, NF-TENG is demonstrated for powering up numerous portable electronics.

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