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 language | English (US) |
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Pages (from-to) | 1101-1105 |
Number of pages | 5 |
Journal | Chinese Pharmacological Bulletin |
Volume | 28 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2012 |
Externally published | Yes |
Keywords
- Cell cycle
- CYP3A4
- DU145 prostate cancer cells
- Gossypol
- Pipeline
- Synergistic effect
ASJC Scopus subject areas
- Pharmacology