title: Auraptene Induces Apoptosis via Myeloid Cell Leukemia 1-Mediated Activation of Caspases in PC3 and DU145 Prostate Cancer Cells.
abstract: Although auraptene, a prenyloxy coumarin from Citrus species, was known to have anti-oxidant, anti-bacterial, antiinflammatory, and anti-tumor activities, the underlying anti-tumor mechanism of auraptene in prostate cancers is not fully understood to date. Thus, in the present study, we have investigated the anti-tumor mechanism of auraptene mainly in PC3 and DU145 prostate cancer cells, because auraptene suppressed the viability of androgen-independent PC3 and DU145 prostate cancer cells better than androgen-sensitive LNCaP cells. Also, auraptene notably increased sub-G1 cell population and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells as features of apoptosis in two prostate cancer cells compared with untreated control. Consistently, auraptene cleaved poly(ADP-ribose) polymerase, activated caspase-9 and caspase-3, suppressed the expression of anti-apoptotic proteins, including Bcl-2 and myeloid cell leukemia 1 (Mcl-1), and also activated pro-apoptotic protein Bax in both prostate cancer cells. However, Mcl-1 overexpression reversed the apoptotic effect of auraptene to increase sub-G1 population and induce caspase-9/3 in both prostate cancer cells. Taken together, the results support scientific evidences that auraptene induces apoptosis in PC3 and DU145 prostate cancer cells via Mcl-1-mediated activation of caspases as a potent chemopreventive agent for prostate cancer prevention and treatment. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of East West Medical Science Graduate School of East West Medical Science, Kyung Hee University, Suwon, Korea.
authors.forename: Jae Chul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Eun Ah
authors.initials: EA
authors.lastname: Shin
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Bonglee
authors.identifier: http://orcid.org/0000-0002-8678-156X
authors.initials: B
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Bo-Im
authors.initials: BI
authors.lastname: Kim
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mahsa
authors.initials: M
authors.lastname: Chitsazian-Yazdi
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Iranshahi
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Sung-Hoon
authors.identifier: http://orcid.org/0000-0003-2423-1973
authors.initials: SH
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D045744:Cell Line, Tumor; D003374:Coumarins / Q000494:pharmacology*; D006801:Humans; D008297:Male; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; D003374:Coumarins; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; C105832:aurapten
keywords: Mcl-1; TUNEL; apoptosis; auraptene; prostate cancer; sub-G1