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Published on: September 8, 2017
Triptolide inhibits the multidrug resistance in prostate cancer cells via the downregulation of MDR1 expression
Abstract:
Triptolide (TPL) is a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii and possesses anti-tumor activity against a range of cancer cells. However, the effect of TPL on prostate cancer cells and its potential to overcome multidrug resistance (MDR) have not been explored. Therefore, in this study we used prostate cancer cell line DU145 as the experimental model and established DU145/ADM cell line resistant to adriamycin (ADM). Our results showed that TPL inhibited the proliferation and induced the cell cycle arrest and apoptosis of DU145 cells in a dose and time dependent manner. TPL decreased the levels of Cyclin D1 and anti-apoptotic protein Bcl-2, and increased the levels of pro-apoptotic proteins Fas and Bax. Furthermore, we found that TPL restored the sensitivity DU145/ADM cells to ADM in a dose dependent manner, and this was accompanied by the inhibition of MDR1 expression at both mRNA and protein levels. Taken together, these results provide strong evidence that TPL overcomes MDR in prostate cancer cells by downregulating MDR1 expression, and suggest that TPL is a promising agent for prostate cancer therapy, especially for chemoresistant prostate cancer.
Insights
Triptolide (TPL) effectively inhibits prostate cancer cell growth and induces apoptosis. It also re-sensitizes multidrug-resistant (MDR) prostate cancer cells to chemotherapy by downregulating MDR1 expression.
Area of Science:
- Pharmacology
- Cancer Biology
- Molecular Oncology
Background:
- Triptolide (TPL), a compound from Tripterygium wilfordii, shows anti-tumor properties.
- The efficacy of TPL against prostate cancer and its ability to overcome multidrug resistance (MDR) remain underexplored.
Purpose of the Study:
- To investigate the effects of TPL on prostate cancer cell proliferation, cell cycle, and apoptosis.
- To determine if TPL can overcome adriamycin (ADM) resistance in prostate cancer cells.
- To elucidate the mechanism by which TPL affects multidrug resistance (MDR).
Main Methods:
- Utilized DU145 prostate cancer cell line and an adriamycin (ADM)-resistant subline (DU145/ADM).
- Assessed TPL's impact on cell proliferation, cell cycle arrest, and apoptosis.
- Quantified changes in key apoptosis-related proteins (Bcl-2, Fas, Bax) and cell cycle regulators (Cyclin D1).
- Evaluated TPL's effect on ADM sensitivity and MDR1 expression at both mRNA and protein levels.
Main Results:
- TPL inhibited DU145 cell proliferation and induced cell cycle arrest and apoptosis in a dose- and time-dependent manner.
- TPL modulated apoptosis-related proteins, decreasing Bcl-2 and increasing Fas and Bax.
- TPL restored sensitivity of DU145/ADM cells to ADM and downregulated MDR1 expression.
Conclusions:
- TPL exhibits significant anti-prostate cancer activity and induces apoptosis.
- TPL effectively overcomes multidrug resistance (MDR) in prostate cancer cells by downregulating MDR1.
- TPL represents a potential therapeutic agent for prostate cancer, particularly for chemoresistant forms.
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