Knockdown of microRNA-29a Changes the Expression of Heat Shock Proteins in Breast Carcinoma MCF-7 Cells

Breast cancer is the most commonly occurring cancer among women. MicroRNAs as noncoding small RNA molecules play pivotal roles in cancer-related biological processes. Increased levels of microRNA-29a in the serum of breast cancer patients have been reported. Since heat shock proteins (HSPs) play important roles in cell events, the quantitative fluctuations in their cellular levels could be deemed as key indicators of how the exerted treatment alters cell behavior. In this regard, using an antisense small RNA, we attempted to investigate the effects of miR-29a knockdown on the expression of HSPs genes in the MCF-7 breast cancer cell line. MCF-7 cells were cultured in high-glucose Dulbecco’s modified Eagle’s medium with 10% FBS. Studied cells were subdivided into five groups: treated with scramble, anti-miR-29a, anti-miR-29a + Taxol, Taxol, and control. Taxol was added 24 h post-anti-miR transfection and RNA extraction, and cDNA synthesis was done 48 h later. The changes in expression of HSP27, HSP40, HSP60, HSP70, and HSP90 were evaluated by real-time PCR. Our results revealed that inhibitors of microRNA-29a promote apoptosis through upregulation of HSP60 level and downregulation of HSP27, HSP40, HSP70, and HSP90 levels and could be contemplated as a compelling alternative for Taxol employment with similar effects and/or to sensitize cancer cells to chemotherapy with fewer side effects

One-pot, four-component synthesis of novel cytotoxic agents 1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines

A series of N-benzyl-1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines were synthesized via one-pot reaction of appropriate benzylamine, pyrrole-2-carbaldehyde, (N-isocyanimino)triphenylphosphorane, and a carboxylic acid. The anti-tumor potential of title compounds was tested against several cancer cell lines by using MTT assay. Some tested compounds including 5e, 5p and 5q exhibited comparable or better cytotoxic activity against A549, HT29 or HT1080 cells in comparison to the reference drug doxorubicin. Also, the cytotoxic activity of compounds 5d and 5n against MCF-7 was better than that of doxorubicin. Compound 5n with IC50 value of 4.3 mM was 4-fold more potent than doxorubicin. The structureeactivity relationship study revealed that the introduction of halogen atoms on both 5-phenyl ring and N-benzyl part improved the cytotoxic activity against all tested cell lines