Plumbagin, a naphthaquinone derivative induces apoptosis in BRCA 1/2 defective castrate resistant prostate cancer cells as well as prostate cancer stem-like cells

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
R S ReshmaPriya Srinivas

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.

References

Dec 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·W H Eschenfeldt, S L Berger
Jun 17, 1998·Nucleic Acids Research·Z KaretsouT Papamarcaki
Feb 18, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alexander LiedeSteven A Narod
Dec 3, 2005·Cancer Research·Anne T CollinsNorman J Maitland
Jul 27, 2006·Neoplasia : an International Journal for Oncology Research·Robert D LobergKenneth J Pienta
Jun 15, 2007·Molecular Carcinogenesis·Sreekala NairM Radhakrishna Pillai
Jul 10, 2007·Toxicology and Applied Pharmacology·Anna KawiakEwa Lojkowska
Aug 28, 2007·Nature Reviews. Cancer·Kristin K DeebCandace S Johnson
Oct 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Shan LuZhongyun Dong
Oct 3, 2008·Molecular Interventions·Brian T KawasakiWilliam L Farrar
Dec 3, 2008·Cancer Research·Donald J Vander GriendJohn T Isaacs
Feb 25, 2009·Current Opinion in Cell Biology·Carl-Henrik HeldinAristidis Moustakas
Nov 10, 2009·Breast Cancer Research and Treatment·Madhuri KakaralaMax S Wicha
Feb 20, 2010·Nature Reviews. Cancer·Dingzhi Wang, Raymond N Dubois
Feb 25, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David G MenterRaymond N DuBois
Apr 15, 2010·The Journal of Clinical Investigation·Penney M GilbertValerie M Weaver
Sep 23, 2010·Nature Reviews. Clinical Oncology·Bostjan SerugaIan F Tannock
May 10, 2011·Cell Stem Cell·Erika PastranaFiona Doetsch
Feb 1, 2012·Molecular Carcinogenesis·Thasni K APriya Srinivas
Jan 17, 2013·World Journal of Gastroenterology : WJG·Yi-Fang Han, Guang-Wen Cao
Apr 6, 2013·Critical Reviews in Eukaryotic Gene Expression·Nicole SalazarBal L Lokeshwar
Apr 10, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Elena CastroRosalind Eeles

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Citations

Sep 22, 2016·Clinical Epigenetics·Inês GraçaCarmen Jerónimo
Apr 1, 2017·The American Journal of Chinese Medicine·Yuling LiuHui Li
Aug 22, 2017·Natural Product Research·Chihiro ItoMasataka Itoigawa
Sep 17, 2017·Oncotarget·Subramanyam DasariGnanasekar Munirathinam
Jul 17, 2018·Oncology Letters·Fengyu HuangXinsheng Wang
Dec 22, 2020·BioMed Research International·Zhenhua YinWenyi Kang
Mar 11, 2021·Cancer Investigation·Prasath ManogaranAnbu Singaravelu

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