3-Oxoolean-12-en-27-oic acid inhibits the proliferation of non-small cell lung carcinoma cells by inducing cell-cycle arrest at G0/G1 phase

Anticancer Res. 2011 Jun;31(6):2179-85.

Abstract

Background: Inhibition of cell-cycle progression is a target for the treatment of cancer. 3-Oxoolean-12-en-27-oic acid (3-OOLA) has shown significant anticancer activity towards diverse cancer cells, but has not been investigated for non-small cell lung carcinoma (NSCLC) cells. In this study, we investigated the antiproliferative effect of 3-OOLA in NSCLC cell lines and its underlying mechanism.

Materials and methods: The MTT assay, bromodeoxyuridine (BrdU) incorporation assay, and flow cytometry were used for cell proliferation studies, and annexin V staining for apoptotic effects. Western blot analysis was used to evaluate expression of cell-cycle regulatory proteins, such as cyclins and cyclin-dependent kinases (CDKs).

Results: 3-OOLA caused G0/G1 phase cell-cycle arrest without inducing apoptosis in NSCLC cells, and Western blot analyses demonstrated down-regulation of cyclin D1, cyclin E and phosphorylated Rb.

Conclusion: 3-OOLA inhibits cell proliferation of NSCLC cells by inducing cell-cycle arrest at G0/G1 through down-regulation of cyclin D1 and cyclin E.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Cyclin D1 / metabolism
  • Cyclin E / metabolism
  • Down-Regulation
  • G1 Phase / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology*
  • Resting Phase, Cell Cycle / drug effects
  • Retinoblastoma Protein / metabolism

Substances

  • 3-oxoolean-12-en-27-oic acid
  • CCND1 protein, human
  • Cyclin E
  • Retinoblastoma Protein
  • Cyclin D1
  • Oleanolic Acid