The natural compound Guttiferone F sensitizes prostate cancer to starvation induced apoptosis via calcium and JNK elevation

BMC Cancer

Xin Li²  Yuanzhi Lao²  Hong Zhang²  Xiaoyu Wang²  Hongsheng Tan²  Zhixiu Lin¹  Hongxi Xu² 

[1] School of Chinese Medicine, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong, SAR, China

[2] Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai 201203, P.R. China

Others  :  1171753
DOI  :  10.1186/s12885-015-1292-z

【 摘 要 】

Background In a cytotoxicity screen in serum-free medium, Guttiferone F showed strong growth inhibitory effect against prostate cancer cells. Methods Prostate cancer cells LNCaP and PC3 were treated with Guttiferone F in serum depleted medium. Sub-G1 phase distributions were estimated with flow cytometry. Mitochondrial disruption was observed under confocal microscope using Mitotracker Red staining. Gene and protein expression changes were detected by real-time PCR and Western blotting. Ca2+ elevation was examined by Fluo-4 staining under fluorescence microscope. PC3 xenografts in mice were examined by immunohistochemical analysis. Results Guttiferone F had strong growth inhibitory effect against prostate cancer cell lines under serum starvation. It induced a significant increase in sub-G1 fraction and DNA fragmentation. In serum-free medium, Guttiferone F triggered mitochondria dependent apoptosis by regulating Bcl-2 family proteins. In addition, Guttiferone F attenuated the androgen receptor expression and phosphorylation of ERK1/2, while activating the phosphorylation of JNK and Ca2+ flux. Combination of caloric restriction with Guttiferone F in vivo could increase the antitumor effect without causing toxicity. Conclusions Guttiferone F induced prostate cancer cell apoptosis under serum starvation via Ca2+ elevation and JNK activation. Combined with caloric restriction, Guttiferone F exerted significant growth inhibition of PC3 cells xenograft in vivo. Guttiferone F is therefore a potential anti-cancer compound.