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Published on: May 11, 2016
Manumycin induces apoptosis in prostate cancer cells
Jing-Gao Li1, Miao-Rong She2, Ci-Yong Lu3
1Department of Nephrology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, China.
Background:
Manumycin exhibits an antitumor effect in a variety of cancer cell lines, including prostate cancer cell lines (DU145 and PC-3). Our previous studies demonstrated that manumycin induced the apoptosis of anaplastic thyroid cancer cells and leukemia cells via the intrinsic apoptosis pathway. In the current study, we further evaluated the effect of manumycin in two prostate cancer cell lines (LNCaP and 22Rv1), and here we elucidate some of the underlying mechanisms.
Materials And Methods:
The cell viability of prostate cancer cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after treatment with manumycin for 48 hours. Apoptosis was detected by flow cytometry using annexin V and propidium iodide. The expressions of B-cell lymphoma (Bcl)-2 family members and the activations of caspase-9 and caspase-3 were detected by Western blotting.
Results:
Manumycin treatment resulted in significant decreases in the viabilities of the two prostate cancer cell lines in a dose-dependent manner through apoptosis, and this apoptosis involved caspase-9 activation. A specific inhibitor of caspase-9 protected cells from caspase-3 activation, apoptosis, and cytotoxicity induced by manumycin. We also found that manumycin downregulated Bcl-2 expression and upregulated Bax expression.
Conclusion:
Our data suggest that manumycin induces apoptosis in prostate cancer cells through regulation of the Bcl-2 family involving caspase-9 activation. These results suggest that manumycin may be beneficial for the treatment of prostate cancer.
Insights
Manumycin induces apoptosis in prostate cancer cells by activating caspase-9 and regulating Bcl-2 family proteins. This suggests manumycin may be a potential treatment for prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Manumycin demonstrates antitumor properties in various cancer cell lines, including prostate cancer.
- Previous research indicated manumycin induces apoptosis in anaplastic thyroid and leukemia cells via the intrinsic pathway.
- This study investigates manumycin's effects on LNCaP and 22Rv1 prostate cancer cell lines.
Purpose of the Study:
- To evaluate the efficacy of manumycin in prostate cancer cell lines.
- To elucidate the underlying molecular mechanisms of manumycin-induced apoptosis in prostate cancer.
Main Methods:
- Cell viability assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.
- Apoptosis detection via flow cytometry (Annexin V/propidium iodide staining).
- Expression of B-cell lymphoma (Bcl)-2 family members and caspase activation (caspase-9, caspase-3) analyzed by Western blotting.
Main Results:
- Manumycin significantly reduced prostate cancer cell viability in a dose-dependent manner, inducing apoptosis.
- Apoptosis was mediated by caspase-9 activation; caspase-9 inhibition prevented manumycin-induced apoptosis and cytotoxicity.
- Manumycin altered Bcl-2 family expression, downregulating Bcl-2 and upregulating Bax.
Conclusions:
- Manumycin induces apoptosis in prostate cancer cells through Bcl-2 family regulation and caspase-9 activation.
- These findings support the potential of manumycin as a therapeutic agent for prostate cancer treatment.

