title: Plumbagin, a naphthaquinone derivative induces apoptosis in BRCA 1/2 defective castrate resistant prostate cancer cells as well as prostate cancer stem-like cells.
abstract: Eventhough the role of BRCA1/2 in hereditary prostatic cancer is being unleashed at a rapid rate; their optimal clinical management remains undefined. Cancer stem cells are thought to be responsible for cancer chemoresistance and relapse, thus they represent a significant concern for cancer prognosis and therapy. In this study, we have analyzed the effect of Plumbagin (PB) and structurally related naphthaquinones on BRCA1/2 silenced prostate cancer cells and the ability of PB to target stem cells. Our cell proliferation studies showed that both PC-3 and DU145 cells were more sensitive to PB, though all the compounds induced mitochondrial potential loss, DNA fragmentation and morphological changes which are indicative of apoptosis. Both BRCA1/2 siRNA transfected PC-3 and DU145 cells exhibited increased sensitivity to PB. Gene expression profiling post PB treatment in BRCA1/2 silenced cells revealed that PB has a putative role in tumor suppression in BRCA defective cancers. Using flow cytometric analysis we have proved that PB has the putative ability to directly target CSCs. Overall studies suggest that PB's antitumour mechanisms holds promise for novel therapeutic approaches against BRCA mutated cancers as well as CSCs.
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: R S
authors.initials: RS
authors.lastname: Reshma
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: K H
authors.initials: KH
authors.lastname: Sreelatha
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India; Center for Cancer Research, National Cancer Institute, Building 567, Room 254, Frederick, MD 21702-1201, United States.
authors.forename: Veena
authors.initials: V
authors.lastname: Somasundaram
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: S
authors.initials: S
authors.lastname: Satheesh Kumar
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: Revathy
authors.initials: R
authors.lastname: Nadhan
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India; Dep. of Surgery, Post Doctoral Research Associate, University of Illinois at Chicago, School of Medicine, 840 South Wood Street, Chicago, IL 60612, United States.
authors.forename: Rakesh Sathish
authors.initials: RS
authors.lastname: Nair
authors.affiliation: Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India. Electronic address: priyasrinivas@rgcb.res.in.
authors.forename: Priya
authors.initials: P
authors.lastname: Srinivas
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D009285:Naphthoquinones / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D009285:Naphthoquinones; C014758:plumbagin
keywords: BRCA1/2; Cancer stem cells; Plumbagin; Prostate cancer