Effects of ganoderma lucidum on cytotoxicity, NRF2/are and heme oxygenase-1 in hepatocellular carcinoma cell-line

Currently, hepatocellular carcinoma (HCC) is the sixth most common cancer in worldwide. However, the studies focusing on molecular etiology of HCC are limited. The Nrf2 signaling pathway provides protection to the cells from different variations of toxic materials and carcinogens via modulating the expression of a number of genes with cytoprotective effects. The Ganoderma lucidum (G. lucidum) has been used in the treatment and prevention of different diseases including cancer. The aim of our study is to evaluate the potential cytotoxic role of G. lucidum in HCC. For this purpose, cell viability assay and analysis of Nrf2-related proteins were done. The most effective concentration of G. lucidum were found at 100 µg/ml. The changes in cytoplasmic/nuclear Nrf2 and HO-1, NQO1 or Keap1 protein levels following G. lucidum extracts (100 or 50 µg/ml) treatments for 24, 48 or 72h were observed. 100 µg/ml concentration of G.lucidum extract inhibits 53% and 59% of cell viability following 24-h and 48-h treatments, respectively. In conclusion, our findings showed that G. lucidum has anti-carcinogenic effects in hepatocellular carcinoma cells. In addition, Nrf2 signaling pathway activation via using phytochemical substances was also shown in this study. Our results also emphasize that it is important to elucidate the underlying molecular mechanisms of Nrf2 activation induced by phytochemicals used in cancer treatment models. KEY WORDS: Ganoderma lucidum, Nrf2/ARE pathway, cytotoxicity, hepatocellular carcinoma cell-line (HCC)