Effects of inotodiol extracts from inonotus obliquus on proliferation cycle and apoptotic gene of human lung adenocarcinoma cell line A549

Chin J Integr Med. 2011 Mar;17(3):218-23. doi: 10.1007/s11655-011-0670-x. Epub 2011 Feb 27.

Abstract

Objective: To observe the proliferation inhibition, apoptosis, and cell proliferation cycle of human lung carcinoma cell line A549 treated with Inotodiol extracts from Inonotus obliquus and explore the possibility of Inotodiol extracts from Inonotus obliquus as a new tumor chemopreventive drug.

Methods: Human lung cancer cell line A549 was treated with different concentrations of Inotodiol, the effects of Inotodiol on cell apoptosis, the expression of Ki-67, Bcl-2, Bax, and p53 and cell cycle were detected by TUNEL assay, immunohistochemistry, and flow cytometry assay respectively.

Results: Inotodiol extracts had antiproliferation effect on human lung carcinoma cell line A549. The expression of Ki-67 decreased with the increase of Inotodiol concentration and exposure time (P<0.05), in a dose-dependent and time-dependent manner. The typical characteristics of the apoptosis of A549 cells treated with Inotodiol were observed, and the apoptotic rate of A549 cell at 48 h was the highest by TUNEL assay. Inotodiol arrested A549 cells in the S phase, and apoptotic peak was observed by flow cytometry. Immunocytochemistry indicated that the expression of Bcl-2 protein decreased, while the expression of p53 and Bax proteins increased in A549 cells treated with Inotodiol, compared with the control cells (P<0.05).

Conclusion: Inotodiol can inhibit proliferation and induce the apoptosis of A549 cells, and its molecular mechanism may be associated with the up-regulating expression of p53 and bax proteins and down-regulating expression of Bcl-2 protein, which arrested A549 cells in S phase.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Basidiomycota / chemistry*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Drug Evaluation, Preclinical
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, bcl-2 / drug effects
  • Genes, p53 / drug effects
  • Humans
  • Ki-67 Antigen / metabolism
  • Lanosterol / analogs & derivatives*
  • Lanosterol / pharmacology
  • Lanosterol / therapeutic use
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Phytotherapy
  • bcl-2-Associated X Protein / genetics

Substances

  • Drugs, Chinese Herbal
  • Ki-67 Antigen
  • bcl-2-Associated X Protein
  • inotodiol
  • Lanosterol