Pyridine analogues of curcumin exhibit high activity for inhibiting CWR-22Rv1 human prostate cancer cell growth and androgen receptor activation

Zhou,Dai‑Ying; Zhao,Su‑Qing; Du,Zhi‑Yun; Zheng,Xi; Zhang,Kun

doi:10.3892/ol.2016.4536

Pyridine analogues of curcumin exhibit high activity for inhibiting CWR-22Rv1 human prostate cancer cell growth and androgen receptor activation

Authors:
- Dai‑Ying Zhou
- Su‑Qing Zhao
- Zhi‑Yun Du
- Xi Zheng
- Kun Zhang
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Affiliations: Guangdong Food and Drug Vocational College, Guangzhou, Guangdong 510520, P.R. China, Institute of Natural Medicinal Chemistry and Green Chemistry, School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China
Published online on: May 6, 2016 https://doi.org/10.3892/ol.2016.4536
Pages: 4160-4166

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Abstract

The concentrations required for curcumin to exert its anticancer activity (IC50, 20 µM) are difficult to achieve in the blood plasma of patients, due to the low bioavailability of the compound. Therefore, much effort has been devoted to the development of curcumin analogues that exhibit stronger anticancer activity and a lower IC50 than curcumin. The present study investigated twelve pyridine analogues of curcumin, labeled as groups AN, BN, EN and FN, to determine their effects in CWR-22Rv1 human prostate cancer cells. The inhibitory effects of these compounds on testosterone (TT)-induced androgen receptor (AR) activity was determined by performing an AR‑linked luciferase assay and by TT‑induced expression of prostate-specific antigen. The results of the current study suggested that the FN group of analogues had the strongest inhibitory effect of growth on CWR‑22Rv1 cultured cells, and were the most potent inhibitor of AR activity compared with curcumin, and the AN, BN and EN analogues. Thus, the results of the present study indicate the inhibition of the AR pathways as a potential mechanism for the anticancer effect of curcumin analogues in human prostate cancer cells. Furthermore, curcumin analogues with pyridine as a distal ring and tetrahydrothiopyran-4-one as a linker may be good candidates for the development of novel drugs for the treatment of prostate cancer, by targeting the AR signaling pathway.

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