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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

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

Authors: Xin Li, Yuanzhi Lao, Hong Zhang, Xiaoyu Wang, Hongsheng Tan, Zhixiu Lin, Hongxi Xu

Published in: BMC Cancer | Issue 1/2015

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Abstract

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.
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Metadata
Title
The natural compound Guttiferone F sensitizes prostate cancer to starvation induced apoptosis via calcium and JNK elevation
Authors
Xin Li
Yuanzhi Lao
Hong Zhang
Xiaoyu Wang
Hongsheng Tan
Zhixiu Lin
Hongxi Xu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1292-z

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