Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 132, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2019.110652
Keywords
Cisplatin; Neferine; Isoliensinine; Colon cancer HCT-15 cells
Categories
Funding
- DST-SERB [SB/SO/HS/075/2013]
- DST-FIST
- UGC-SAP
Ask authors/readers for more resources
Cisplatin (CDDP) is a potent platinum-based chemotherapeutic agent used to treat solid tumors including colorectal cancer via inducing cytotoxicity. CDDP usage is limited due to the chemoresistance and associated adverse effects. A combinatorial regimen of phytochemicals with anticancer activity along with approved anticancer drugs seems to be a hopeful strategy against cancer treatment. Lotus-derived compounds such as neferine and isoliensinine have proven significant chemosensitizing activity in different cancer cells. Present study aims to compare chemosensitizing activity/anticancer potential of neferine/isoliensinine in combinatorial regimen with CDDP. Results documented that neferine/isoliensinine with CDDP augmented 'intracellular uptake of cisplatin' consequently apoptosis in HCT-15 cells exemplified by 'apoptotic morphological changes', 'S phase cell cycle arrest', 'ROS mediated oxidative stress' with the concomitant escalation in intracellular calcium & dissipation of MMP and activation of MAPK/PI3K/AKT pathway'. Furthermore, isoliensinine combination with CDDP exclusively enhanced CDDP uptake and induced more ROS-mediated apoptosis compared to other treatment regimens. Combination regimens induced downregulation of Bcl2 and upregulation of cytochrome c, caspase 3, 9, PARP cleavage indicating apoptosis induction through the intrinsic pathway. Thus, the results of the present study suggest that CDDP combination with neferine/isoliensinine augments the anticancer potential of CDDP in an additive manner and decrease CDDP dose requirement.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available