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

Abstract

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.

Coronarin D induces human oral cancer cell apoptosis though upregulate JNK1/2 signaling pathway

“…Apoptosis is a molecularly programmed cell death with the key elements of death receptors, membrane alterations, protease cascade, mitochondrial changes, and DNA fragmentation . Consistent with other research that has been conducted on CD, our results also showed that CD induced cell G2/M arrest, and altered the mitochondrial membrane potential, all of them involving apoptosis (Figures ).…”

“…Coronarin D derived from the roots of Hedychium coronarium , exhibits promising anti‐proliferative, pro‐apoptotic, anti‐invasive, and anti‐angiogenetic effects and is a potential natural anti‐cancer agent for nasopharyngeal carcinoma and human hepatocellular carcinoma . However, the definite effects of CD against human oral cancer are uncertain currently.…”

“…CD was also known to have anti‐proliferative, pro‐apoptotic, anti‐invasive, anti‐angiogenic, anti‐osteoclastogenic, and anti‐inflammatory effects through the suppression of NF‐ĸB and NF‐ĸB‐regulated gene products . Studies in recent years have shown that CD is a potential anticancer agent for nasopharyngeal carcinoma and human hepatocellular carcinoma . However, the effectiveness of CD action in oral cancer still remains unclear.…”

Coronarin D Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Line

“…Many natural products can suppress proliferation by arresting cells at phases in the cell cycle [25]. The p21 is a small protein with 165 amino acids and belongs to the CIP/Kip family of CDK inhibitors.…”

“…Further, Coronarin D exhibits antiproliferative, pro-apoptotic, anti-invasive, antiangiogenic, antiosteoclast, and anti-inflammatory activity by suppressing NF-κB and the gene products regulated by this pathway of osteoclastogenesis [24]. Recently, Coronarin D has been described as inducing apoptosis in human hepatocellular carcinoma (HCC) [25] and in human oral cancer (OSCC) [26] through the c-Jun N-terminal kinases (JNK) pathway while it has induced reactive oxygen species-mediated cell death in human nasopharyngeal cancer cells (NPC) through inhibition of p38 mitogen-activated protein kinase (MAPK) and activation of JNK [27].…”