Neferine and isoliensinine enhance 'intracellular uptake of cisplatin' and induce 'ROS-mediated apoptosis' in colorectal cancer cells - A comparative study

Food Chem Toxicol. 2019 Oct:132:110652. doi: 10.1016/j.fct.2019.110652. Epub 2019 Jun 27.

Abstract

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.

Keywords: Cisplatin; Colon cancer HCT-15 cells; Isoliensinine; Neferine.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Benzylisoquinolines / pharmacology*
  • Cell Line, Tumor
  • Cisplatin / metabolism
  • Cisplatin / pharmacology*
  • Drug Combinations
  • Drug Synergism
  • Humans
  • Isoquinolines / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Reactive Oxygen Species / metabolism*

Substances

  • Antineoplastic Agents
  • Benzylisoquinolines
  • Drug Combinations
  • Isoquinolines
  • Reactive Oxygen Species
  • isoliensinine
  • neferine
  • Cisplatin