title: Plumbagin Inhibits Prostate Carcinogenesis in Intact and Castrated PTEN Knockout Mice via Targeting PKCε, Stat3, and Epithelial-to-Mesenchymal Transition Markers.
abstract: Prostate cancer continues to remain the most common cancer and the second leading cause of cancer-related deaths in American males. The Pten deletions and/or mutations are frequently observed in both primary prostate cancers and metastatic prostate tissue samples. Pten deletion in prostate epithelium in mice results in prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma. The Pten conditional knockout mice [(Pten-loxp/loxp:PB-Cre4(+)) (Pten-KO)] provide a unique preclinical model to evaluate agents for efficacy for both the prevention and treatment of prostate cancer. We present here for the first time that dietary plumbagin, a medicinal plant-derived naphthoquinone (200 or 500 ppm) inhibits tumor development in intact as well as castrated Pten-KO mice. Plumbagin has shown no signs of toxicity at either of these doses. Plumbagin treatment resulted in a decrease expression of PKCε, AKT, Stat3, and COX2 compared with the control mice. Plumbagin treatment also inhibited the expression of vimentin and slug, the markers of epithelial-to-mesenchymal transition (EMT) in prostate tumors. In summary, the results indicate that dietary plumbagin inhibits growth of both primary and castration-resistant prostate cancer (CRPC) in Pten-KO mice, possibly via inhibition of PKCε, Stat3, AKT, and EMT markers (vimentin and slug), which are linked to the induction and progression of prostate cancer.
authors: Department of Human Oncology, Wisconsin Institute for Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin. hafeez@humonc.wisc.edu.
authors: Bilal Bin
authors: BB
authors: Hafeez
authors: Department of Human Oncology, Wisconsin Institute for Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
authors: Joseph W
authors: JW
authors: Fischer
authors: Department of Human Oncology, Wisconsin Institute for Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
authors: Ashok
authors: A
authors: Singh
authors: Department of Pathology, Wisconsin Institute for Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
authors: Weixiong
authors: W
authors: Zhong
authors: Department of Human Oncology, Wisconsin Institute for Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
authors: Ala
authors: A
authors: Mustafa
authors: Department of Human Oncology, Wisconsin Institute for Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
authors: Louise
authors: L
authors: Meske
authors: Department of Human Oncology, Wisconsin Institute for Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
authors: Mohammad Ozair
authors: MO
authors: Sheikhani
authors: Department of Human Oncology, Wisconsin Institute for Medical Research, Paul Carbone Comprehensive Cancer Center, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin.
authors: Ajit Kumar
authors: AK
authors: Verma
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D063646:Carcinogenesis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009285:Naphthoquinones / Q000494:pharmacology* / Q000627:therapeutic use; D009919:Orchiectomy; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019048:Prostatic Intraepithelial Neoplasia / Q000188:drug therapy / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015415:Biomarkers; D009285:Naphthoquinones; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D051744:Protein Kinase C-epsilon; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; C014758:plumbagin
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