Resveratrol Arrests Cell Cycle and Induces Apoptosis in Human Hepatocellular Carcinoma Huh-7 Cells

Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan.
Journal of medicinal food (Impact Factor: 1.7). 10/2010; 13(6):1415-23. DOI: 10.1089/jmf.2010.1126
Source: PubMed

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Autophagy is a complicated self-eating response of cells to external or internal stimuli. This process involves cellular degradation through the lysosomes of dysfunctional or unnecessary cellular components or organelles to maintain basic energy levels. This nonapoptotic programmed cell death, similar to other main phenomena of cell biology such as apoptosis and differentiation, has been implicated in the pathogenesis of a series of disorders, such as neurodegenerative diseases, cardiovascular diseases, and especially in cancer. Increasing evidence has suggested that the autophagy pathways may provide potential targets for cancer intervention, although their precise roles in cancer initiation and progression remain controversial. Natural products are very important sources of chemotherapeutics agents. Regulation of autophagy could be an important mechanism contributing to the beneficial effect of quite a few natural products. Herein, we briefly introduce the characteristics and roles of autophagy in cancer and systematically summarize the natural autophagy regulators, with emphasis on apigenin, berberine, beta-elemene, capsaicin, curcumin, genistein, kaempferol, oridonin, paclitaxel, quercetin, resveratrol, silybin, triptolide, and ursolic acid, with the aim to provide information for novel avenues on cancer therapies based on autophagy.
    Phytochemistry Reviews 02/2014; 14(1). DOI:10.1007/s11101-014-9339-3 · 2.89 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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:10.4103/2225-4110.114895
  • Source
    [Show abstract] [Hide abstract]
    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