期刊
ENVIRONMENTAL TOXICOLOGY
卷 37, 期 5, 页码 995-1006出版社
WILEY
DOI: 10.1002/tox.23459
关键词
caffeic acid phenethyl ester; DNA damage; metastasis; prostate cancer; radiation
资金
- Council of Scientific and Industrial Research India [09/265(1059) 2015 EMR-1]
- Jawaharlal Nehru University
In this study, the radiomodulatory potential of caffeic acid phenethyl ester (CAPE) in prostate cancer cells was evaluated. CAPE was found to enhance the sensitivity of prostate cancer cells to radiation and induce apoptosis, while inhibiting cell migration. The combination treatment of CAPE and radiation increased DNA damage and cell death by inhibiting DNA repair proteins. Therefore, CAPE may be a potential adjuvant for the treatment of hormone-refractory radioresistant prostate cancer.
In the present study, we evaluated the radiomodulatory potential of caffeic acid phenethyl ester (CAPE), an active component of traditional herbal medicine propolis. CAPE has been identified as a potent anticancer agent in multiple cancer types and is reported to have the dual role of radioprotection and radiosensitization. However, the radiomodulatory potential of CAPE in prostate cancer (PCa), which eventually becomes radioresistant is not known. Therefore, we studied the effect of co-treatment of CAPE and gamma radiation on androgen-independent DU145 and PC3 cells. The combination treatment sensitized PCa cells to radiation in a dose-dependent manner. The radiosensitizing effect of CAPE was observed in both cell lines. CAPE enhanced the level of ionizing radiation (IR)-induced gamma H2AX foci and cell death by apoptosis. The combination treatment also decreased the migration potential of PCa cells. This was confirmed by increased expression of E-cadherin and decrease in vimentin expression. CAPE sensitized PCa cells to radiation in vitro and induced apoptosis, augmented phosphorylation of Akt/mTOR, and hampered cell migration. At the mechanistic level, co-treatment of CAPE and IR inhibited cell growth by decreasing RAD50 and RAD51 proteins involved in DNA repair. This resulted in enhanced DNA damage and cell death. CAPE might represent a promising new adjuvant for the treatment of hormone-refractory radioresistant PCa.
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