In Vitro and In Vivo Antitumor Effects of Pyrimethamine on Non-small Cell Lung Cancers

doi:10.21873/anticanres.12612

CNU IR > Pharmacy and Science > Dept. of Pharmacy > Periodical Articles > Item 310902800/32222

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Title:	In Vitro and In Vivo Antitumor Effects of Pyrimethamine on Non-small Cell Lung Cancers
Authors:	Lin, Meng-Xian Lin, Sheng-Hao Lin, Chi-Chen Yang, Ching-Chieh Yuan, Sheau-Yun
Contributors:	Natl Chung Hsing Univ, Inst Biomed Sci Changhua Christian Hosp, Dept Internal Med, Div Chest Med Chi Mei Med Ctr, Dept Radiat Oncol Natl Sun Yat Sen Univ, Inst Biomed Sci Chia Nan Univ Pharm & Sci, Dept Pharm Taichung Vet Gen Hosp, Dept Med Res Hungkuang Univ, Dept Nursing
Keywords:	Non-small cell lung cancer (NSCLC) pyrimethamine cell cycle apoptosis mitochondrial damage
Date:	2018-06
Issue Date:	2019-11-15 15:45:44 (UTC+8)
Publisher:	INT INST ANTICANCER RESEARCH
Abstract:	Background/Aim: Pyrimethamine (PYR), an antimalarial drug is known to inhibit various types of human cancer cells. The aim of this study was to investigate the anti-tumour effects of pyrimethamine (PYR) and its underlying molecular mechanisms using the human NSCLC cell line A549. Materials and Methods: PYR was dissolved in dimethyl sulfoxide to determine its apoptotic activity on A549 cells. Cell viability was determined by the MTT assay. Cell cycle, mitochondrial membrane potential, and Annexin V-FITC early apoptosis detection were evaluated by flow cytometry. Cyclin-dependent kinase (CDK) and Bcl-2 family protein expression was determined by western blotting. Results: PYR reduced cell viability percentage and induced G(0)/G(1) arrest, which was associated with down-regulation of cyclins D1 and E, CDK4, and CDK2, and up-regulation of p21. PYR induced sub-G(1) accumulation, Annexin-V binding, caspase-9 and -3 activation, poly (ADPribose) polymerase cleavage, and mitochondrial dysfunction in A549 cells. Moreover, PYR effectively inhibited NSCLC tumour growth in an A549 xenograft model. Conclusion: PYR demonstrated anti-tumour effects on NSCLC in vitro and in vivo, indicating its therapeutic potential against human NSCLC.
???metadata.dc.relation.uri???:	http://dx.doi.org/10.21873/anticanres.12612
Relation:	Anticancer Research, v.38, n.6, pp.3435-3445
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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