Combination of curcumin and bicalutamide enhanced the growth inhibition of androgen-independent prostate cancer cells through SAPK/JNK and MEK/ERK1/2-mediated targeting NF-κB/p65 and MUC1-C

Journal of Experimental & Clinical Cancer Research

Swei Sunny Hann¹  ZhiQiang Chen²  LiJun Yang³  JianFu Zhou²  Qing Tang³  JingJing Wu³  QiouHong Zhang²  SongTao Xiang²  Jing Li² 

[1] Higher Education Mega Center, Panyu District, Guangdong Provincial Hospital of Chinese Medicine, No. 55, Neihuan West Road, Guangzhou 510006, Guangdong Province, People’s Republic of China;Department of Urology Surgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical Collage, University of Guangzhou Traditional Chinese Medicine, Guangzhou 510120, Guangdong Province, China;Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical Collage, University of Guangzhou Traditional Chinese Medicine, Guangzhou 510120, Guangdong Province, China

关键词: MUC1-C;    NF-κB/p65;    SAPK/JNK;    Bicalutamide;    Curcumin;    Androgen-independent prostate cancer cells;   

Others  :  1220702
DOI  :  10.1186/s13046-015-0168-z

 received in 2015-03-04, accepted in 2015-05-08,  发布年份 2015

【 摘 要 】

Background

Prostate cancer is one of the most common malignancies in men. The mucin 1 (MUC1) heterodimeric oncoprotein is overexpressed in human prostate cancers with aggressive pathologic and clinical features, resulting in a poor outcome. However, the functional role for MUC1 C-terminal domain (MUC1-C) in androgen-independent prostate cancer occurrence and development has remained unclear.

Methods

Cell viability was measured by MTT assays. Western blot analysis was performed to measure the phosphorylation and protein expression of SAPK/JNK and ERK1/2, and MUC1-C, NF-κB subunit p65 and p50. Exogenous expression of MUC1-C, NF-κB subunit p65 was carried out by transient and electroporated transfection assays.

Results

We showed that curcumin inhibited the growth of androgen-independent prostate cancer cells and a synergy was observed in the presence of curcumin and bicalutamide, the androgen receptor antagonist. To further explore the potential mechanism underlining this, we found that curcumin increased the phosphorylation of ERK1/2 and SAPK/JNK, which was enhanced by bicalutamide. In addition, curcumin reduced the protein expression of MUC1-C and NF-κB subunit p65, which were abrogated in the presence of the inhibitors of MEK/ERK1/2 (PD98059) and SAPK/JNK (SP60015). A further reduction was observed in the combination of curcumin with bicalutamide. Moreover, while exogenous expression of MUC1-C had little effect on curcumin-reduced p65, the overexpression of p65 reversed the effect of curcumin on MUC1-C protein expression suggesting that p65 is upstream of MUC1-C. Intriguingly, we showed that exogenous expression of MUC1-C feedback diminished the effect of curcumin on phosphorylation of ERK1/2 and SAPK/JNK, and antagonized the effect of curcumin on cell growth.

Conclusion

Our results show that curcumin inhibits the growth of androgen-independent prostate cancer cells through ERK1/2- and SAPK/JNK-mediated inhibition of p65, followed by reducing expression of MUC1-C protein. More importantly, there are synergistic effects of curcumin and bicalutamide. The negative feedback regulatory loop of MUC1-C to ERK1/2 and SAPK/JNK further demonstrates the role of MUC1-C that contributes to the overall responses of curcumin. This study unveils the potential molecular mechanism by which combination of curcumin with bicalutamide enhances the growth inhibition of androgen-independent prostate cancer cells.

【 授权许可】

   
2015 Li et al.; licensee BioMed Central.

【 图 表 】

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