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

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 cy...

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Autores principales: Li, Xin, Lao, Yuanzhi, Zhang, Hong, Wang, Xiaoyu, Tan, Hongsheng, Lin, Zhixiu, Xu, Hongxi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394563/
https://www.ncbi.nlm.nih.gov/pubmed/25885018
http://dx.doi.org/10.1186/s12885-015-1292-z
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author Li, Xin
Lao, Yuanzhi
Zhang, Hong
Wang, Xiaoyu
Tan, Hongsheng
Lin, Zhixiu
Xu, Hongxi
author_facet Li, Xin
Lao, Yuanzhi
Zhang, Hong
Wang, Xiaoyu
Tan, Hongsheng
Lin, Zhixiu
Xu, Hongxi
author_sort Li, Xin
collection PubMed
description 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. Ca(2+) 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 Ca(2+) 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 Ca(2+) 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1292-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-43945632015-04-14 The natural compound Guttiferone F sensitizes prostate cancer to starvation induced apoptosis via calcium and JNK elevation Li, Xin Lao, Yuanzhi Zhang, Hong Wang, Xiaoyu Tan, Hongsheng Lin, Zhixiu Xu, Hongxi BMC Cancer Research Article 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. Ca(2+) 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 Ca(2+) 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 Ca(2+) 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1292-z) contains supplementary material, which is available to authorized users. BioMed Central 2015-04-11 /pmc/articles/PMC4394563/ /pubmed/25885018 http://dx.doi.org/10.1186/s12885-015-1292-z Text en © Li et al.; licensee BioMed Central. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Li, Xin
Lao, Yuanzhi
Zhang, Hong
Wang, Xiaoyu
Tan, Hongsheng
Lin, Zhixiu
Xu, Hongxi
The natural compound Guttiferone F sensitizes prostate cancer to starvation induced apoptosis via calcium and JNK elevation
title The natural compound Guttiferone F sensitizes prostate cancer to starvation induced apoptosis via calcium and JNK elevation
title_full The natural compound Guttiferone F sensitizes prostate cancer to starvation induced apoptosis via calcium and JNK elevation
title_fullStr The natural compound Guttiferone F sensitizes prostate cancer to starvation induced apoptosis via calcium and JNK elevation
title_full_unstemmed The natural compound Guttiferone F sensitizes prostate cancer to starvation induced apoptosis via calcium and JNK elevation
title_short The natural compound Guttiferone F sensitizes prostate cancer to starvation induced apoptosis via calcium and JNK elevation
title_sort natural compound guttiferone f sensitizes prostate cancer to starvation induced apoptosis via calcium and jnk elevation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394563/
https://www.ncbi.nlm.nih.gov/pubmed/25885018
http://dx.doi.org/10.1186/s12885-015-1292-z
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