title: 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.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China. lixin458468@126.com.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China. lixin458468@126.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China. Laurence_ylao@163.com.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China. Laurence_ylao@163.com.
authors.forename: Yuanzhi
authors.initials: Y
authors.lastname: Lao
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China. zhnjau19851010@163.com.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China. zhnjau19851010@163.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China. wangdxiaoyu@hotmail.com.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China. wangdxiaoyu@hotmail.com.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China. ths97029@163.com.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China. ths97029@163.com.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Tan
authors.affiliation: School of Chinese Medicine, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong, SAR, China. linzx@cuhk.edu.hk.
authors.forename: Zhixiu
authors.initials: Z
authors.lastname: Lin
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, P.R. China. xuhongxi88@gmail.com.|Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, P.R. China. xuhongxi88@gmail.com.
authors.forename: Hongxi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001577:Benzophenones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D031204:Caloric Restriction; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001577:Benzophenones; D001688:Biological Products; D019253:Proto-Oncogene Proteins c-bcl-2; D011944:Receptors, Androgen; C117502:guttiferone F; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases; D002118:Calcium