The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells

Toxicol Appl Pharmacol. 2011 Aug 1;254(3):221-8. doi: 10.1016/j.taap.2011.03.016. Epub 2011 Mar 30.

Abstract

Despite a lack of scientific authentication, Scutellaria baicalensis is clinically used in Chinese medicine as a traditional adjuvant to chemotherapy of lung cancer. In this study, cytotoxicity assays demonstrated that crude ethanolic extracts of S. baicalensis were selectively toxic to human lung cancer cell lines A549, SK-LU-1 and SK-MES-1 compared with normal human lung fibroblasts. The active compounds baicalin, baicalein and wogonin did not exhibit such selectivity. Following exposure to the crude extracts, cellular protein expression in the cancer cell lines was assessed using 2D gel electrophoresis coupled with MALDI-TOF-MS/Protein Fingerprinting. The altered protein expression indicated that cell growth arrest and apoptosis were potential mechanisms of cytotoxicity. These observations were supported by PI staining cell cycle analysis using flow cytometry and Annexin-V apoptotic analysis by fluorescence microscopy of cancer cells treated with the crude extract and pure active compounds. Moreover, specific immunoblotting identification showed the decreased expression of cyclin A results in the S phase arrest of A549 whereas the G(0)/G(1) phase arrest in SK-MES-1 cells results from the decreased expression of cyclin D1. Following treatment, increased expression in the cancer cells of key proteins related to the enhancement of apoptosis was observed for p53 and Bax. These results provide further insight into the molecular mechanisms underlying the clinical use of this herb as an adjuvant to lung cancer therapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Cell Cycle / drug effects*
  • Cell Cycle / genetics
  • Cell Line
  • Cell Line, Tumor
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology*
  • Ethanol / pharmacology
  • Humans
  • Lung Neoplasms* / chemistry
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / pathology
  • Scutellaria baicalensis*
  • Tumor Suppressor Protein p53 / biosynthesis*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • bcl-2-Associated X Protein / biosynthesis*

Substances

  • BAX protein, human
  • Drugs, Chinese Herbal
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Ethanol