title: The inhibition of PI3K and NFκB promoted curcumin-induced cell cycle arrest at G2/M via altering polyamine metabolism in Bcl-2 overexpressing MCF-7 breast cancer cells.
abstract: Bcl-2 protein has been contributed with number of genes which are involved in oncogenesis. Among the many targets of Bcl-2, NFκB have potential role in induction of cell cycle arrest. Curcumin has potential therapeutic effects against breast cancer through multiple signaling pathways. In this study, we investigated the role of curcumin in induction of cell cycle arrest via regulating of NFκB and polyamine biosynthesis in wt and Bcl-2+ MCF-7 cells. To examine the effect of curcumin on cell cycle regulatory proteins, PI3K/Akt, NFκB pathways and polyamine catabolism, we performed immunoblotting assay. In addition, cell cycle analysis was performed by flow cytometry. The results indicated that curcumin induced cell cycle arrest at G2/M phase by downregulation of cyclin B1 and Cdc2 and inhibited colony formation in MCF-7wt cells. However, Bcl-2 overexpression prevented the inhibition of cell cycle associated proteins after curcumin treatment. The combination of LY294002, PI3K inhibitor, and curcumin induced cell cycle arrest by decreasing CDK4, CDK2 and cyclin E2 in Bcl-2+ MCF-7 cells. Moreover, LY294002 further inhibited the phosphorylation of Akt in Bcl-2+ MCF-7 cells. Curcumin could suppress the nuclear transport of NFκB through decreasing the interaction of P-IκB-NFκB. The combination of wedelolactone, NFκB inhibitor, and curcumin acted different on SSAT expression in wt MCF-7 and Bcl-2+ MCF-7 cells. NFκB inhibition increased the SSAT after curcumin treatment in Bcl-2 overexpressed MCF-7 cells. Inhibition of NFκB activity as well as suppression of ROS generation with NAC resulted in the partial relief of cells from G2/M checkpoint after curcumin treatment in wt MCF-7 cells. In conclusion, the potential role of curcumin in induction of cell cycle arrest is related with NFκB-regulated polyamine biosynthesis.
authors.affiliation: Istanbul Kultur University, Dept. of Molecular Biology and Genetics, Atakoy Campus, 34156 Istanbul, Turkey.
authors.forename: Özge
authors.initials: Ö
authors.lastname: Berrak
authors.affiliation: Istanbul Kultur University, Dept. of Molecular Biology and Genetics, Atakoy Campus, 34156 Istanbul, Turkey.
authors.forename: Yunus
authors.initials: Y
authors.lastname: Akkoç
authors.affiliation: Istanbul Kultur University, Dept. of Molecular Biology and Genetics, Atakoy Campus, 34156 Istanbul, Turkey. Electronic address: d.arisan@iku.edu.tr.
authors.forename: Elif Damla
authors.initials: ED
authors.lastname: Arısan
authors.affiliation: Istanbul Kultur University, Dept. of Molecular Biology and Genetics, Atakoy Campus, 34156 Istanbul, Turkey.
authors.forename: Ajda
authors.initials: A
authors.lastname: Çoker-Gürkan
authors.affiliation: Istanbul Kultur University, Dept. of Molecular Biology and Genetics, Atakoy Campus, 34156 Istanbul, Turkey.
authors.forename: Pınar
authors.initials: P
authors.lastname: Obakan-Yerlikaya
authors.affiliation: Istanbul Kultur University, Dept. of Molecular Biology and Genetics, Atakoy Campus, 34156 Istanbul, Turkey.
authors.forename: Narçin
authors.initials: N
authors.lastname: Palavan-Ünsal
mesh_terms: D000123:Acetyltransferases / Q000096:biosynthesis; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation; D002470:Cell Survival; D002867:Chromones / Q000494:pharmacology; D003374:Coumarins / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints; D019254:Genes, bcl-2 / Q000235:genetics*; D006801:Humans; D061986:MCF-7 Cells; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000096:biosynthesis*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis*; D011073:Polyamines / Q000378:metabolism*; D015398:Signal Transduction; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D002867:Chromones; D003374:Coumarins; D003474:Curcumin; D009025:Morpholines; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D011073:Polyamines; D000099228:Diamine N-Acetyltransferase; C051122:wedelolactone; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: Bcl-2; Cell cycle; Curcumin; NFκB