Synergistic inhibition of growth of prostate cancer DU145 cells by combined piperine and gossypol treatment

Long Hui Zeng, Li Hui Xu, Xian Hui He, Dong Yun Ou-Yang, Yan Ting Zhang, Shuai Ren

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Aim: To investigate the effect of combined pipeline and gossypol in inhibition of the growth of androgen-independent prostate cancer DU145 cells and elucidate the underlying mechanism. Methods: MTS assay was adopted to measure the cell viability. Cell cycle distribution was analyzed by flow cytometry. Western blotting was used to determine the expression of cell cycle related proteins and CYP3A4. Results: Piperine was relatively low toxic to DU145 cells, whereas when it was used in combination with gossypol, the IC50 of gossypol was decreased from 21.00 μmol·L-1 to 8.07 μmol·L-1. The coefficient of drug interaction was less than 1, demonstrating that pipeline plus gossypol had a synergistic effect on inhibition of the growth of DU145 cells. The combined drugs also significantly arrested cells at G0/G1 phase, and increased sub-G 0/G1 peak (apoptotic peak). Moreover, the combined pipeline and gossypol also results in an increased level of p21Cip1 expression and decreased expression levels of Cyclin D1, Cyclin A, Cyclin B1 and drug-metabolic enzyme CYP3A4. Conclusion: The combination of pipeline and gossypol results in synergistic inhibition of DU145 cell growth through induction of cell cycle arrest, increase of cell apoptosis and inhibition of CYP3A4 activity.

Original languageEnglish (US)
Pages (from-to)1101-1105
Number of pages5
JournalChinese Pharmacological Bulletin
Volume28
Issue number8
DOIs
StatePublished - Aug 2012
Externally publishedYes

Keywords

  • Cell cycle
  • CYP3A4
  • DU145 prostate cancer cells
  • Gossypol
  • Pipeline
  • Synergistic effect

ASJC Scopus subject areas

  • Pharmacology

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