guttiferone-f and Prostatic-Neoplasms

In a cytotoxicity screen in serum-free medium, Guttiferone F showed strong growth inhibitory effect against prostate cancer cells.. 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.. 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.. 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.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Benzophenones; Biological Products; Calcium; Caloric Restriction; Caspases; Cell Line, Tumor; Cell Proliferation; Cytosol; Disease Models, Animal; Humans; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Signaling System; Mice; Mitochondria; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2; Receptors, Androgen; Xenograft Model Antitumor Assays