Assessment of anti-cancerous potential of 6-gingerol (Tongling White Ginger) and its synergy with drugs on human cervical adenocarcinoma cells

Food Chem Toxicol. 2017 Nov;109(Pt 2):910-922. doi: 10.1016/j.fct.2017.02.038. Epub 2017 Feb 27.

Abstract

The anti-cancerous activity of 6-gingerol extracted from Tongling White Ginger was investigated. 6-Gingerol inhibited the growth of HeLa cells with IC50 (96.32 μM) and IC80 (133.01 μM) and led to morphological changes, induced the cell cycle arrest in G0/G1-phase and ultimately resulted into apoptosis. Among cell cycle-related genes and proteins, the expression of cyclin (A, D1, E1) reduced, while of CDK-1, p21 and p27 showed slight decrease, except cyclin B1 and E1 (protein). Western blotting reported the induction of apoptosis with an increased Bax/Bcl-2 ratio, release of cytochrome c, cleavage of caspase-3, -8, -9 and PRPP in treated cells. 6-Gingerol activated AMPK, but inhibited PI3K/AKT phosphorylation with reduced P70S6K expression and also suppressed the mTOR phosphorylation. 6-Gingerol with 5-FU and Ptx resulted in 83.2% and 52% inhibition respectively, this synergy have stimulated apoptosis proteins more efficiently as compared to 6-Gingerol alone (10.75%) under in vitro conditions.

Keywords: 6-Gingerol; Anti-cancerous activities; Combination; Tongling White Ginger.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / physiopathology
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Catechols / pharmacology*
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Evaluation, Preclinical
  • Drug Synergism
  • Fatty Alcohols / pharmacology*
  • Female
  • Fluorouracil / pharmacology
  • Humans
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / physiopathology
  • Zingiber officinale / chemistry*

Substances

  • Antineoplastic Agents
  • Catechols
  • Fatty Alcohols
  • gingerol
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Caspase 3
  • Fluorouracil