Coronarin D induces apoptotic cell death through the JNK pathway in human hepatocellular carcinoma

: Coronarin D, a diterpene derived from the rhizomes of Hedychium coronarium, has been used to treat inflammatory diseases. Coronarin D can exert strong anticancer effects through cell growth prevention and cell cycle arrest in many cancer cells. In this study, we investigated the molecular mechanism through which coronarin D suppresses cell proliferation and triggers cell death in human hepatocellular carcinoma (HCC) cells. Treatment of Huh7 and Sk-hep-1 cells with coronarin D resulted in a significantly increased loss of mitochondrial membrane potential, leading to the cleavage and activation of caspase-9, caspase-8, and caspase-3 and changes in Bax, Bcl-2, and Bcl-xL protein levels. Coronarin D significantly induced autophagy by increasing the expression of Beclin-1 and LC3-II and reducing the expression of p62. Moreover, Huh7 and Sk-hep-1 cells exposed to coronarin D had decreased expression of phosphorylated AKT, p38, and ERK and increased expression of phosphorylated JNK. Exposure of cells to the JNK-specific inhibitor SP600125 attenuated the apoptotic effects of coronarin D. Taken together, this is the first study to report that coronarin D may effectively inhibit cell growth through apoptosis. We have provided evidence indicating that coronarin D induces cell death through the upregulation of JNK mitogen-activated protein kinases in human HCC cells.