Elettaria Cardamom Extract Synergistically Enhaning Sorafenib-Induced Apoptosis in HepG2 Cells

Introduction: Liver cancer is ranked as the second most common cause of death globally as a result of its poor prognosis. It can be treated with sorafenib, but its use is limited due to its toxicity and adverse reactions. Lower doses of sorafenib with other complementary agents are recommended to minimize toxicity. Cardamom seeds are one of the most common ingredients of Indian and Chinese traditional medicine, and different studies have suggested that cardamom extract can display anti-cancer activities. Aim: this study aims to investigate the efficiency of Elettaria Cardamom Extract (ECE) on enhancement of Sorafenib-induced apoptosis in HepG2. Methods: Human liver cancer cell line (HepG2) were exposed to increasing concentrations of individual and combined treatments of Sorafenib and ECE for 24 h. The viability of cells was examined using MTT Assay. Clonogenicity and cell migration assays were carried out. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) level were determined by DCFH-DA and JC-1 dye, respectively. Agarose gel electrophoresis and comet examinations were carried out to estimate the DNA damage. Results: Combined treatment of ECE with sorafenib suppressed the proliferation, colony formation and cell migration of HepG2 cells more than the sorafenib did alone. The half maximal inhibitory concentration (IC50), after 24h of incubation were 15 mu M of sorafenib and 9 and 7.3 mu M of sorafenib enhanced by 5 and 10 mu g / 100 mu l of ECE respectively. HepG2 treated cells displayed biochemical features of apoptotic cell death. The combined treatment increased the ROS production, reduced the level of MMP, increased Comet tail length and induced DNA fragmentation more than sorafenib did alone. Conclusions: These findings demonstrate that ECE enhanced the sorafenib effect in HepG2 cells and suggest that the ECE may be a promising agent for reducing sorafenib side effects in hepatocellular carcinoma (HCC).