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

Anticancer Research
Meng-Xian LinSheau-Yun Yuan

Abstract

Pyrimethamine (PYR), an anti-malarial 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. 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. PYR reduced cell viability percentage and induced G0/G1 arrest, which was associated with down-regulation of cyclins D1 and E, CDK4, and CDK2, and up-regulation of p21. PYR induced sub-G1 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. PYR demonstrated anti-tumour effects on NSCLC in vitro and in vivo, indicating its therapeutic potential against human NSCLC.

Citations

Jun 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dae Gyu KimSunkyung Lee
Aug 12, 2021·OncoTargets and Therapy·Siou-Min LuoDueng-Yuan Hueng
Dec 19, 2021·IUBMB Life·Shanaya RamchandaniKwang Seok Ahn

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