Sahin, KazimTuzcu, MehmetYabas, MehmetOrhan, CemalSahin, NurhanOzercan, Ibrahim H.2024-06-122024-06-1220180167-69971573-0646https://doi.org/10.1007/s10637-017-0540-2https://hdl.handle.net/20.500.14551/22117The goals of the present study were to define the anticancer activity of LFM-A13 (alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)-propenamide), a potent inhibitor of Polo-like kinase (PLK), in a mouse mammary cancer model induced by 7,12-dimethylbenz(a)anthracene (DMBA) in vivo and explore its anticancer mechanism(s). We also examined whether the inhibition of PLK by LFM-A13 would improve the efficiency of paclitaxel in breast cancer growth in vivo. To do this, female BALB/c mice received 1 mg of DMBA once a week for 6 weeks with oral gavage. LFM-A13 (50 mg/kg body weight) was administered intraperitoneally with DMBA administration and continued for 25 weeks. We found that LFM-A13, paclitaxel, and their combination have a significant effect on the DMBA-induced breast tumor incidence, mean tumor numbers, average tumor weight, and size. At the molecular level, the administration of LFM-A13 hindered mammary gland carcinoma development by regulating the expression of PLK1, cell cycle-regulating proteins cyclin D1, cyclin dependent kinase-4 (CDK-4), and the CDK inhibitor, p21. Moreover, LFM-A 13 treatment upregulated the levels of I kappa B, the pro-apoptotic proteins Bax, and caspase-3, and down-regulated p53 and the antiapoptotic protein Bcl-2 in mammary tumors. The combination of LFM-A13 with paclitaxel was found to be more effective compared with either agent alone. Collectively, these results suggest that LFM-A13 has an anti-proliferative activity against breast cancer in vivo and that LFM-A13 and paclitaxel combination could be a strategy for the treatment of breast cancer.en10.1007/s10637-017-0540-2info:eu-repo/semantics/closedAccessLFM-A13Mammary CarcinogenesisPLKDMBACancerExpressionPaclitaxelEfficacyProfileTargetPlk1P21PrkBtkArticle363388395Q2WOS:0004319549000042-s2.0-8503372262229139009Q1