Molecular and cellular pharmacologyGalangin inhibits proliferation of HepG2 cells by activating AMPK via increasing the AMP/TAN ratio in a LKB1-independent manner
Introduction
Ferlay et al. (2010) and Cauchy et al. (2012) have reported that hepatocellular carcinoma (HCC) is one of the most common cancers. Although chemotherapy is a common therapeutic strategy after surgery, its use has been limited due to its toxicity to normal tissues. Therefore, it is important to screen for new nontoxic anti-cancer drugs. Natural products have been used for preventing cancer for centuries and are thus envisioned as safer alternatives for their chemical counterparts (Surh, 2003). Some dietary compounds possess anti-cancer properties such as suppressing cell proliferation and inducing cell death. Natural compounds are therefore used to enhance the efficacy of chemotherapeutic agents (Surh, 2003).
Alpinia officinarum Hance is used as a traditional Chinese medicine and about 90% Alpinia officinarum Hance in China is from Zhanjiangin regions. Galangin is a polyphenolic compound derived primarily from the rhizome of Alpinia officinarum Hance\ (Heo et al., 2001). The molecular weight of galangin is about 270.24 Da. We have shown that galangin significantly decreases cell viability and induces apoptosis of hepatocellular carcinoma cells (HCC) lines and suggested that galangin may be a potential anti-HCC agent (Zhang et al., 2012). Furthermore, a report by Wen et al. (2012) have described galangin-induced intracellular vacuolation in HepG2 cell and suggested that these vacuoles represent autophagic vesicles. These observations suggest that galangin may inhibit the proliferation of HepG2 cells by a novel mechanism. However, the precise mechanism by which galangin induces autophagy remains unclear. In this study, we demonstrated the effects of galangin on HCC cells and elucidated the mechanism by which galangin inhibits HepG2 cell proliferation.
Section snippets
Cell culture
Three human liver cancer cell lines HepG2, Hep3B, and PLC/PRF/5 were kept in the Institute of Biochemistry and Molecular Biology in Guangdong Medical College. The cell lines were cultured in the Dulbecco's modified Eagle medium (Gibco BRL) supplemented with 10% fetal bovine serum, 100 μg/ml of penicillin, and 100 μg/ml of streptomycin. The cells were incubated at 37 °C in a humidified atmosphere with 5% CO2.
Agents and chemicals
Galangin (PubChem CID: 5281616) was purchased from Sigma-Aldrich and dissolved in dimethyl
Inhibition of HCC proliferation by galangin in vitro
To explore the effect of galangin on hepatoma proliferation, three hepatoma cell lines were treated with galangin for 24 h and cell viability was measured using the MTT assay. Our results showed that after being treated with galangin, cell survival decreased in a dose-dependent manner (Fig. 1A). Additionally, colony formation assay showed similar results (Fig. 1B). Galangin exhibited significant inhibition of cell proliferation at a concentration range of 5–40 μM in the colony formation assay.
Discussion
Galangin is a bioflavonoid found in Alpinia officinarum Hance or honey, which have been used as dietary factors and herbal medicine for centuries in China (Heo et al., 2001). Previous reports have demonstrated that galangin possesses anti-HCC activity by inducing apoptosis (Zhang et al., 2012) or autophagy (Wen et al., 2012). In this study, as galangin induced the extensive autophagysome formation, activated AMPK was observed in galangin-treated HepG2 cells.
Autophagy is an ancient cell survival
Acknowledgments
This Project was supported by the National Natural Science Foundation of China (Grant no. 81273549), Science and Technology Projects of Guangdong Province, China (No. 2011B031700057), Guangdong Natural Science Foundation (No. S2011010004076), and Science and Technological Program for Dongguan's Higher Education, Science and Research, and Health Care Institutions (2012108102051) and Team Building Project of Doctoral Construction of Guangdong Medical College.
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