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

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. 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.

• Authors: Xin Li, Yuanzhi Lao, Hong Zhang, Xiaoyu Wang, Hongsheng Tan, Zhixiu Lin, Hongxi Xu
• Journal: BMC cancer (BMC Cancer) Vol. 15 Pg. 254 (Apr 11 2015) ISSN: 1471-2407 [Electronic] England
• PMID: 25885018 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Benzophenones
• Biological Products
• Proto-Oncogene Proteins c-bcl-2
• Receptors, Androgen
• guttiferone F
• JNK Mitogen-Activated Protein Kinases
• Caspases
• Calcium

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, chemistry, pharmacology)
• Apoptosis (drug effects)
• Benzophenones (administration & dosage, chemistry, pharmacology)
• Biological Products (administration & dosage, chemistry, pharmacology)
• Calcium (metabolism)
• Caloric Restriction
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cytosol (metabolism)
• Disease Models, Animal
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• MAP Kinase Signaling System (drug effects)
• Male
• Mice
• Mitochondria (drug effects, metabolism)
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Receptors, Androgen (metabolism)
• Xenograft Model Antitumor Assays