title: Polyamine depletion enhances the roscovitine-induced apoptosis through the activation of mitochondria in HCT116 colon carcinoma cells.
abstract: Small molecule inhibitors of cyclin-dependent kinases (CDKs) show high therapeutic potential in various cancer types which are characterized by the accumulation of transformed cells due to impaired apoptotic machinery. Roscovitine, a CDK inhibitor showed to be a potent apoptotic inducer in several cancer cells. Polyamines, putrescine, spermidine and spermine, are biogenic amines involved in many cellular processes, including apoptosis. In this study, we explored the potential role of polyamines in roscovitine-induced apoptosis in HCT116 colon cancer cells. Roscovitine induced apoptosis by activating mitochondrial pathway caspases and modulating the expression of Bcl-2 family members. Depletion of polyamines by treatment with difluoromethylornithine (DFMO) increased roscovitine-induced apoptosis. Transient silencing of ornithine decarboxylase, polyamine biosynthesis enzyme and special target of DFMO also increased roscovitine-induced apoptosis in HCT116 cells. Interestingly, additional putrescine treatment was found pro-apoptotic due to the presence of non-functional ornithine decarboxylase (ODC). Finally, roscovitine altered polyamine catabolic pathway and led to decrease in putrescine and spermidine levels. Therefore, the metabolic regulation of polyamines may dictate the power of roscovitine induced apoptotic responses in HCT116 colon cancer cells.
authors.affiliation: Molecular Biology and Genetics Department, Istanbul Kultur University, Science and Literature Faculty, Atakoy Campus, 34156, Istanbul, Turkey.
authors.forename: Elif Damla
authors.initials: ED
authors.lastname: Arısan
authors.forename: Ajda
authors.initials: A
authors.lastname: Coker
authors.forename: Narçin
authors.initials: N
authors.lastname: Palavan-Ünsal
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015317:Biogenic Polyamines / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011687:Purines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077546:Roscovitine
chemical_list: D000970:Antineoplastic Agents; D015317:Biogenic Polyamines; D011687:Purines; D017382:Reactive Oxygen Species; D000077546:Roscovitine