10-Gingerol, a Phytochemical Derivative from "Tongling White Ginger", Inhibits Cervical Cancer: Insights into the Molecular Mechanism and Inhibitory Targets

J Agric Food Chem. 2017 Mar 15;65(10):2089-2099. doi: 10.1021/acs.jafc.7b00095. Epub 2017 Mar 1.

Abstract

With the aim of evaluating anticancerous activities of 10-gingerol (10-G) against HeLa cells, it was purified and identified from "Tongling white ginger" by HSCCC, UPLC-TOF-MS/MS, and NMR analysis, respectively. 10-G inhibited the proliferation of HeLa cells at IC50 (29.19 μM) and IC80 (50.87 μM) with altered cell morphology, increased cytotoxicity, and arrested cell cycle in the G0/G1 phase. Most cell cycle related genes and protein expression significantly decreased, followed by a slight decrease in a few without affecting cyclin B1 and cyclin E1 (protein). Both death receptors significantly up-regulated and activated apoptosis indicators (caspase family). Furthermore, significant changes in mitochondria-dependent pathway markers were observed and led to cell death. 10-G led to PI3K/AKT inhibition and AMPK activation to induce mTOR-mediated cell apoptosis in HeLa cells. These results can be an asset to exploit 10-G with other medicinal plant derivatives for future applications.

Keywords: 10-gingerol; HeLa cells; PI3K/AKT/AMPK/mTOR pathways; Tongling white ginger; apoptosis.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Catechols / chemistry
  • Catechols / pharmacology*
  • Cell Cycle Checkpoints / drug effects
  • Cell Proliferation / drug effects
  • Cyclin E / genetics
  • Cyclin E / metabolism
  • Fatty Alcohols / chemistry
  • Fatty Alcohols / pharmacology*
  • Female
  • HeLa Cells
  • Humans
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Tandem Mass Spectrometry
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / physiopathology
  • Zingiber officinale / chemistry*

Substances

  • Antineoplastic Agents
  • Catechols
  • Cyclin E
  • Fatty Alcohols
  • Plant Extracts
  • gingerol
  • Phosphatidylinositol 3-Kinases