Anti-cancer effects of dioscin on three kinds of human lung cancer cell lines through inducing DNA damage and activating mitochondrial signal pathway

Food Chem Toxicol. 2013 Sep:59:118-28. doi: 10.1016/j.fct.2013.05.054. Epub 2013 Jun 11.

Abstract

Dioscin, a natural steroid saponin, has been widely investigated. However, its anti-cancer activities on human lung cancer cells are still unknown. In the present paper, the inhibitory effects of dioscin were investigated, and the results showed that dioscin inhibited the proliferation of human A549, NCI-H446 and NCI-H460 cancer cells. DNA damage and cell apoptosis in dioscin-treated cells were found through single cell gel electrophoresis and in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. Furthermore, dioscin caused mitochondrial structure changes and blocked cell cycle at S phase based on transmission electron microscope and flow cytometry analysis. In addition, dioscin treatment caused the release of cytochrome c from mitochondria into cytosol. The activities of Caspase-3 and -9 in dioscin-treated groups were significantly increased compared with control group. Western blotting analysis showed that dioscin significantly down-regulated the expressions of Bcl-2 and Bcl-xl, and up-regulated the expressions of Bax, Bak and Bid. Our results indicate that dioscin has anticancer activities against human lung cancer cells through inducing cell cycle arrest, DNA damage and activating mitochondrial signal pathway.

Keywords: Anti-cancer; DNA damage; Dioscin; Human lung cancer cell lines; Mitochondrial pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / ultrastructure
  • Adenocarcinoma of Lung
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / agonists
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Apoptosis Regulatory Proteins / metabolism
  • Carcinoma, Large Cell / drug therapy
  • Carcinoma, Large Cell / metabolism
  • Carcinoma, Large Cell / ultrastructure
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Cytosol / ultrastructure
  • DNA Damage*
  • Diosgenin / analogs & derivatives*
  • Diosgenin / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / ultrastructure
  • Microscopy, Electron, Transmission
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure
  • Protein Transport / drug effects
  • S Phase / drug effects
  • Signal Transduction / drug effects*
  • Small Cell Lung Carcinoma / drug therapy
  • Small Cell Lung Carcinoma / metabolism
  • Small Cell Lung Carcinoma / ultrastructure

Substances

  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • dioscin
  • Diosgenin