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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[1]	Siegel RL,Miller KD,Jemal A.Cancer Statistics,2016[J].CA Cancer J Clin,2016,66(1):7-30.
[2]	Gao Y.Development and health economic evaluation of breast cancer screening strategy among Chinese women(中国女性乳腺癌筛查策略优化研究及卫生经济学评价)[D].Tianjin:Tianjin Medical University,2016.
[3]	Liu S,Zhao J,Liu J,et al.Effects of Ru′ai Shuhou Recipe on 5-year recurrence rate after mastectomy in breast cancer[J].J Chin Integr Med(中西医结合学报),2008,10:1001-1004.
[4]	Hahne JC,Lampis A,Meyer S,et al.Role of PI3K/AKT-signaling pathway in triple-negative breast cancer[C].4th World Congress on Breast Pathology and Cancer Diagnosis,2017.
[5]	Tomao F,Papa A,Zaccarelli E,et al.Triple-negative breast cancer:new perspectives for targeted therapies[J].Oncol Targets Ther,2015,8:177-193.
[6]	Costa R,Han HS,Gradishar WJ.Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer:a review[J].Breast Cancer Res Treat,2018,169:397-406.
[7]	Zhou XL,Wang RZ,Zhou K,et al.Novel compound 1 inhibits the viability of triple negative breast MDA-MB-231 cells via the PI3K/AKT/mTOR pathway[J].Acta Med Univ Sci Technol Huazhong(华中科技大学学报医学版),2017,46(2):127-132.
[8]	Oliveira LPD,Carneiro ZA,Ribeiro CM,et al.Three new platinum complexes containing fluoroquinolones and DMSO:cytotoxicity and evaluation against drug-resistant tuberculosis[J].J Inorg Biochem,2018,183:77-83.
[9]	Sankaran M,Chandraprakash K,Uvarani C,et al.A convenient method of facilitating Aryl-Aryl bond-formation reactions in the synthesis of biquinoline- and quinoline-bearing chromene derivatives[J].Cheminform,2013,44(14):2858-2864.
[10]	Epifano F,Genovese S,Rosati O,et al.Ytterbium triflate catalyzed synthesis of β-functionalized indole derivatives[J].Tetrahedr Lett,2011,52(5):568-571.
[11]	Bello C,Bai J,Zambron BK,et al.Induction of cell killing and autophagy by amphiphilic pyrrolidine derivatives on human pancreatic cancer cells[J].Eur J Med Chem,2018,150:457-478.
[12]	Qin S,Yang C,Huang W,et al.Sulforaphane attenuates microglia-mediated neuronal necroptosis through down-regulation of MAPK/NF-κB signaling pathways in LPS-activated BV-2 microglia[J].Pharmacol Res,2018,133:325-326.
[13]	Park J,Lee YR,Shim HJ,et al.Control of tumor suppressor protein PTEN by dimethlysulfoxide in HL-60 cells[J].J Clin Oncol,2004,22(14):3156-3156.
[14]	Hers I,Vincent EE,Tavara JM.Akt signalling in health and disease[J].Cell Signal,2011,23(10):1515-1527.
[15]	Tuo Y,Xiang M.mTOR:a double-edged sword for diabetes[J].J Leukocyte Biol,2018,3:21-29.
[16]	Cao C,Zhang HN,Yang ZL,et al.Peptide recognition,signaling and modulation of class B G protein-coupled receptors[J].Curr Opin Struc Biol,2018,51:53-60.
[17]	Indio V,Astolfi A,Tarantino G,et al.Integrated molecular characterization of gastrointestinal stromal tumors(GIST)harboring the rare D842V mutation in PDGFRA gene[J].Int J Mol Sci,2018,19(3):732-747.
[18]	Araldi D, Ferrari LF, Levine JD. Role of GPCR(mu-opioid)-receptor tyrosine kinase(epidermal growth factor)crosstalk in opioid-induced hyperalgesic priming(type II)[J].Pain,2018,159(5):864-875.
[19]	Wu Q,Chen JX,Chen Y,et al.The chemokine receptor CCR10 promotes inflammation-driven hepatocarcinogenesis via PI3K/Akt pathway activation[J].Cell Death Dis,2018,9(2):232-249.
[20]	Yu ST,Zhong Q,Chen RH,et al.CRLF1 promotes malignant phenotypes of papillary thyroid carcinoma by activating the MAPK/ERK and PI3K/AKT pathways[J].Cell Death Dis,2018,9(3):371-383.
[21]	Clement E,Inuzuka H,Nihira N,et al.Skp2-dependent reactivation of AKT drives resistance to PI3K inhibitors[J].Sci Signal,2018,11(521):eaao3810.
[22]	Li Z,Wu Y,Chen H,et al.MTOR suppresses environmental particle-induced inflammatory response in macrophages[J].J Immunol,2018,200(8):2826-2834.
[23]	Liu YY,Chen MB,Cheng L,et al.microRNA-200a downregulation in human glioma leads to Gαi1 over-expression,Akt activation,and cell proliferation[J].Oncogene,2018,37(21):2890-2902.
[24]	Dazert E,Hall MN.mTOR signaling in disease[J].Curr Opin Cell Biol,2011,23(6):744-755.
[25]	Mi C,Ma J,Wang KS,et al.Imperatorin suppresses proliferation and angiogenesis of human colon cancer cell by targeting HIF-1α via the mTOR/p70S6K/4E-BP1 and MAPK pathways[J].J Ethnopharmacol,2017,203:27-38.
[26]	Haupt Y,Maya R,Kazaz A,et al.MDM2 promotes the rapid degradation of p53[J].Nature,1997,387(6630):296-299.
[27]	Li Y,Stockton ME,Bhuiyan I,et al.MDM2 inhibition rescues neurogenic and cognitive deficits in a mouse model of fragile X syndrome[J].Sci Transl Med,2016,8(336):336ra61.
[28]	Zhou BP,Liao Y,Xia W,et al.HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation[J].Nat Cell Biol,2001,3(11):973-982.
[29]	Choy MK,Movassagh M,Bennett MR,et al.PKB/Akt activation inhibits p53-mediated HIF1A degradation that is independent of MDM2[J].J Cell Physiol,2010,222(3):635-639.

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