Corilagin in Cancer: A Critical Evaluation of Anticancer Activities and Molecular Mechanisms.

Corilagin (ß-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), an ellagitannin, is one of the major bioactive compounds present in various plants. Ellagitannins belong to the hydrolyzable tannins, a group of polyphenols. Corilagin shows broad-spectrum biological, and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, and antitumor actions. Natural compounds possessing antitumor activities have attracted significant attention for treatment of cancer. Corilagin has shown inhibitory activity against the growth of numerous cancer cells by prompting cell cycle arrest at the G2/M phase and augmented apoptosis. Corilagin-induced apoptosis and autophagic cell death depends on production of intracellular reactive oxygen species in breast cancer cell line. It blocks the activation of both the canonical Smad and non-canonical extracellular-signal-regulated kinase/Akt (protein kinase B) pathways. The potential apoptotic action of corilagin is mediated by altered expression of procaspase-3, procaspase-8, procaspase-9, poly (ADP ribose) polymerase, and Bcl-2 Bax. In nude mice, corilagin suppressed cholangiocarcinoma growth and downregulated the expression of Notch1 and mammalian target of rapamycin. The aim of this review is to summarize the anticancer efficacy of corilagin with an emphasis on the molecular mechanisms involving various signaling pathways in tumor cells.

Chetomin induces apoptosis in human triple-negative breast cancer cells by promoting calcium overload and mitochondrial dysfunction.

Human triple-negative breast cancer (TNBC) is poorly diagnosed and unresponsive to conventional hormone therapy. Chetomin (CHET), a fungal metabolite synthesized by Chaetomium cochliodes, has been reported as a promising anticancer and antiangiogenic agent but the complete molecular mechanism of its anticancer potential remains to be elucidated. In our study, we explored the anti-neoplastic action of CHET on TNBC cells. Cytotoxicity studies were performed in human TNBC cells viz. MDA-MB-231 and MDA-MB-468 cells by Sulforhodamine B assay. It exhibited antiproliferative response and induced apoptosis in both the cell types. Cell cycle analysis revealed that it increases the sub G0/G1 phase cell population. Modulation of mitochondrial membrane potential, activation of caspase 3/7 and a remarkable increase in the expression of cleaved PARP and increased chromatin condensation was observed after CHET treatment in MDA-MB-231 and MDA-MB-468 cells. Additionally, an elevated level of intracellular Ca2+ played an important role in CHET mediated cell death response. Calcium overload in mitochondria led to release of cytochrome c which in turn triggered caspase-3 mediated cell death. Inhibition of calcium signalling using BAPTA-AM reduced apoptosis confirming the involvement of calcium signalling in CHET induced cell death. Chetomin also inhibited PI3K/mTOR cell survival pathway in human TNBC cells. The overall findings suggest that Chetomin inhibited the growth of human TNBC cells by caspase-dependent apoptosis and modulation of PI3K/mTOR signalling and could be used as a novel chemotherapeutic agent for the treatment of human TNBC in future.