Coronarin D induces reactive oxygen species-mediated cell death in human nasopharyngeal cancer cells through inhibition of p38 MAPK and activation of JNK

Abstract

Background and PurposeNasopharyngeal carcinoma (NPC) belongs to squamous cell carcinoma that occurs in the epithelial lining of the nasopharynx. Because of the anatomical position close to the cervical lymph node, some patients have a distant metastasis at the time of diagnosis that leads to treatment failure. Although early stages have a high curability and excellent prognosis, advanced NPC urgently requires new drugs developed to reinforce the effectiveness of therapy without noticeable side effects.Experimental approachCoronarin D (CD), a natural product extracted from the rhizomes of Hedychium coronarium, has been reported to possess anticancer potential. The aim of the present study was to determine the anticancer activity of CD and further elucidate the underlying molecular mechanisms.Key ResultsIn this study, we first demonstrated that CD potently suppressed cell viability in various NPC cell lines. Treatment of cells with CD induced G2/M arrest, apoptosis, and autophagy. Further studies showed that CD increased the production of reactive oxygen species and subsequently activated both autophagy and apoptosis. Moreover, we found that CD-induced activation of p38 and JNK constituted major mechanisms involved in the apoptosis and autophagy triggered by CD. In particular, inhibition of autophagy could strengthen the cytotoxicity of CD, implying that autophagy seems to play a valuable survival and protective role in cancer cells.Conclusions & ImplicationsThese findings provide a promise for the use of CD in combination with autophagy inhibitors for treatment of human NPC cell lines.

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

“…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].…”

The Ginger Prophecy; A Review of the Underexplored Genus, Hedychium against Cancer

“…coronarin D has been shown to constrain the activation of the NF-kB pathway induced by different carcinogens and pro-inflammatory molecules and also debilitate the expression of constitutive NF-kB [95] . Chen and co-workers [96] reported that coronarin D induced ROS-mediated death in human nasopharyngeal cells by activating JNK along with inhibition of p38 MAPK whereas Giron and co-workers [95] found that coronarin D inhibits NF-kB also by down regulating IKK activation.…”