Resveratrol Arrests Cell Cycle and Induces Apoptosis in Human Hepatocellular Carcinoma Huh-7 Cells
ABSTRACT Resveratrol has been shown to possess anticancer, anti-aging, anti-inflammatory, antimicrobial, and neuroprotective activities. In this study, we examined the antiproliferative properties of resveratrol and its molecular mechanism(s) of action in Huh-7 cells, a new human hepatoma cell line system for hepatitis C virus. Results showed that resveratrol significantly inhibited Huh-7 cell proliferation (50% inhibitory concentration = 22.4 μg/mL) and effectively induced cell cycle arrest and apoptosis. It up-regulated p21/WAF1 expression in a p53-independent manner, but the expressions of cyclin E, cyclin A, and cyclin-dependent kinase 2 were down-regulated. It also caused an increase in the ratio of pro-apoptotic/anti-apoptotic protein, which was associated with the mitochondrial membrane depolarization and the increase in caspase activity. Resveratrol showed no effect on Fas, Fas ligand, extracellular signal regulated kinase (ERK) 1/2, and p38 expression but down-regulated phospho-ERK and phospho-p38 expression. In addition, resveratrol was noted to trigger autophagic cell death through the increased expression of autophagy-related Atg5, Atg7, Atg9, and Atg12 proteins. These results suggest that resveratrol could be an important chemoprevention agent for hepatoma of hepatitis C virus infection.
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ABSTRACT: Cancer is one of the deadliest diseases against humans. To tackle this menace, humans have developed several high-technology therapies, such as chemotherapy, tomotherapy, targeted therapy, and antibody therapy. However, all these therapies have their own adverse side effects. Therefore, recent years have seen increased attention being given to the natural food for complementary therapy, which have less side effects. Garlic (Dà Suàn; Allium sativum), is one of most powerful food used in many of the civilizations for both culinary and medicinal purpose. In general, these foods induce cancer cell death by apoptosis, autophagy, or necrosis. Studies have discussed how natural food factors regulate cell survival or death by autophagy in cancer cells. From many literature reviews, garlic could not only induce apoptosis but also autophagy in cancer cells. Autophagy, which is called type-II programmed cell death, provides new strategy in cancer therapy. In conclusion, we wish that garlic could be the pioneer food of complementary therapy in clinical cancer treatment and increase the life quality of cancer patients.03/2013; 3(3):159-162. DOI:10.4103/2225-4110.114895This article is viewable in ResearchGate's enriched formatRG Format enables you to read in context with side-by-side figures, citations, and feedback from experts in your field.
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ABSTRACT: 14-3-3 proteins are implicated in the regulation of proteins involved in a variety of signaling pathways. 14-3-3-dependent protein regulation occurs through phosphorylation-dependent binding that results, in many cases, in the release of survival signals in cells. Autophagy is a cell digestion process that contributes to overcoming nutrient deprivation and is initiated under stress conditions. However, whether autophagy is a cell survival or cell death mechanism remains under discussion and may depend on context. Nevertheless, autophagy is a cellular process that determines cell fate and is tightly regulated by different signaling pathways, some of which, for example MAPK, PI3K and mTOR, are tightly regulated by 14-3-3 proteins. It is therefore important to understand the role of 14-3-3 protein in modulating the autophagic process. Within this context, direct binding of 14-3-3 to mTOR regulatory proteins, such as TSC2 and PRAS40, connects 14-3-3 with autophagy regulatory processes. In addition, 14-3-3 binding to human vacuolar protein sorting 34 (hVps34), a class III phosphatidylinositol-3-kinase (PI3KC3), indicates the involvement of 14-3-3 proteins in regulating autophagosome formation. hVps34 is involved in vesicle trafficking processes such as autophagy, and its activation is needed for initiation of autophagy. Chromatography and overlay techniques suggest that hVps34 directly interacts with 14-3-3 proteins under physiological conditions, thereby maintaining hVps34 in an inactive state. In contrast, nutrient starvation promotes dissociation of the 14-3-3–hVps34 complex, thereby enhancing hVps34 lipid kinase activity. Thus, 14-3-3 proteins are regulators of autophagy through regulating key components of the autophagic machinery. This review summarizes the role of 14-3-3 protein in the control of target proteins involved in regulating the master switches of autophagy.12/2012; 1(4):754-73. DOI:10.3390/cells1040754
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ABSTRACT: Autophagy, a lysosomal degradation pathway for cellular constituents and organelles, is an adaptive and essential process required for cellular homeostasis. Although autophagy functions as a survival mechanism in response to cellular stressors such as nutrient or growth factor deprivation, it can also lead to a non-apoptotic form of programmed cell death (PCD) called autophagy-induced cell death or autophagy-associated cell death (type II PCD). Current evidence suggests that cell death through autophagy can be induced as an alternative to apoptosis (type I PCD), with therapeutic purpose in cancer cells that are resistant to apoptosis. Thus, modulating autophagy is of great interest in cancer research and therapy. Natural polyphenolic compounds that are present in our diet, such as rottlerin, genistein, quercetin, curcumin, and resveratrol, can trigger type II PCD via various mechanisms through the canonical (Beclin-1 dependent) and non-canonical (Beclin-1 independent) routes of autophagy. The capacity of these compounds to provide a means of cancer cell death that enhances the effects of standard therapies should be taken into consideration for designing novel therapeutic strategies. This review focuses on the autophagy- and cell death-inducing effects of these polyphenolic compounds in cancer.Cell Death & Disease 11/2014; 5:e1509. DOI:10.1038/cddis.2014.467 · 5.18 Impact Factor