Dipyridyl pyrrolidine inhibits MDA-MB231 breast cancer cell cycle by inhibiting AKT-mTOR

YAN Liang; ZAN Jiawei; FENG Zunyong; MA Jinzhu; XU Lei; WANG Yi

doi:10.11665/j.issn.1000-5048.20180613

Journal of China Pharmaceutical University > 2018 > 49(6): 718-824. > DOI: 10.11665/j.issn.1000-5048.20180613

YAN Liang, ZAN Jiawei, FENG Zunyong, MA Jinzhu, XU Lei, WANG Yi. Dipyridyl pyrrolidine inhibits MDA-MB231 breast cancer cell cycle by inhibiting AKT-mTOR[J]. Journal of China Pharmaceutical University, 2018, 49(6): 718-824. DOI: 10.11665/j.issn.1000-5048.20180613

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Dipyridyl pyrrolidine inhibits MDA-MB231 breast cancer cell cycle by inhibiting AKT-mTOR

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Abstract

To investigate the induction of cell cycle arrest of human breast cancer MDA-MB231 cells by Di-indolyl pyrrolidine(DIPRD), a pyrrolidine-derived spirooxindoles compounds. The cytotoxic effect of DIPRD on MDA-MB231 cells was detected by CCK-8 method. The cell cycle arrest of MDA-MB231 cells was detected by DAPI/EdU double-staining. Phosphorylation levels of AKT, mTOR, apoptosis-related proteins p53, MDM2, and DNA repair enzyme PARP levels were detected by Western blot. DIPRD inhibited the viability of MDA-MB231 cells by downregulating the number of EdU-positive cells, increase G₁ phase and reduce cell number in S/G₂ phase, down-regulated the p-AKT(Ser473), p-mTOR, p-p53, cyclin D1, CDK4, and the upregulated the p-AKT(Thr308), p-MDM2 and Cleaved-PARP levels were detected in a dose-dependent manner at 12. 5, 25, and 50 mg/mL. DIPRD may play a role in cell cycle arrest through AKT signaling pathway and induce cell apoptosis.
- dipyridyl pyrrolidine,
- breast cancer,
- MDA-MB231 cells,
- cell cycle

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Dipyridyl pyrrolidine inhibits MDA-MB231 breast cancer cell cycle by inhibiting AKT-mTOR

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