title: Berbamine inhibited the growth of prostate cancer cells in vivo and in vitro via triggering intrinsic pathway of apoptosis.
abstract: Berbamine (BBM) has been reported with antitumor activities. BBM inhibited the growth of prostate cancer (PCa) cells and caused vacuolization of mitochondria in preliminary study. We hypothesized BBM could enhance apoptosis of PCa cells through mitochondrial pathway.
  
  
  
  Growth of PC-3 and LNCaP cells treated by BBM was determined by cell viability assay. The morphology of mitochondria was observed by electron microscopy. Apoptosis was quantified by flow cytometry. Expressions of bax/bcl-2, active caspase-9 and active caspase-3 were examined by western blot and real-time PCR. Methazolamide, an inhibitor of cytochrome c, was added to examine its blockade effect on BBM. PC-3 cells were injected subcutaneously into athymic mice, and BBM or saline was administrated intravenously. Diameters of induced tumors were compared, and ratios of apoptotic cells in tumor tissues were calculated.
  
  
  
  BBM inhibited viability of cultured PC-3 and LNCaP cells in dose- and time-dependent manners. Flow cytometry showed BBM induced apoptosis in cultured cells. Mitochondria showed swelling, vacuolization and fused mitochondrial cristae. Western blot and real-time PCR analysis both showed increases of bax/bcl-2, active caspase-9 and active caspase-3. Methazolamide impeded effect of BBM on inducing apoptosis of cultured cells, and activations of caspase-9 and caspase-3 were also inhibited. Growth of tumors by grafted PC-3 cells was significantly slower in BBM group. Ratios of apoptotic cells in tumors were significantly higher in BBM group. Expressions of active caspase-9 and active caspase-3 in tumors were significantly upregulated by BBM.
  
  
  
  BBM exhibited strong anti-PCa activities in vitro and in vivo relying on activating caspase-3 via intrinsic pathway of apoptosis, holding a great promise to develop new strategies for PCa.
authors.affiliation: Minimally Invasive Urology Center, Shandong Provincial Hospital affiliated with Shandong University, Jinan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Urology, Shandong Provincial Hospital affiliated with Shandong University, Jinan, China.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lv
authors.affiliation: Minimally Invasive Urology Center, Shandong Provincial Hospital affiliated with Shandong University, Jinan, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: Minimally Invasive Urology Center, Shandong Provincial Hospital affiliated with Shandong University, Jinan, China.
authors.forename: X B
authors.initials: XB
authors.lastname: Jin
authors.affiliation: Minimally Invasive Urology Center, Shandong Provincial Hospital affiliated with Shandong University, Jinan, China.
authors.forename: M W
authors.initials: MW
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shandong Provincial Hospital affiliated with Shandong University, Jinan, China.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Su
authors.affiliation: Center of Electron Microscopy, School of Medicine, Shandong University, Jinan, China.
authors.forename: L Y
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Minimally Invasive Urology Center, Shandong Provincial Hospital affiliated with Shandong University, Jinan, China.|Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: H Y
authors.initials: HY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D044182:Benzylisoquinolines; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053453:Caspase 9; C027870:berbamine