Meng-Xian Lin1, Sheng-Hao Lin1,2, Chi-Chen Lin1, Ching-Chieh Yang3,4,5, Sheau-Yun Yuan6,7. 1. Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan, R.O.C. 2. Department of Internal Medicine, Division of Chest Medicine, Changhua Christian Hospital, Changhua, Taiwan, R.O.C. 3. Department of Radiation Oncology, Chi Mei Medical Center, Tainan, Taiwan, R.O.C. yuan5805@gmail.com cleanclear0905@gmail.com. 4. Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan, R.O.C. 5. Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, R.O.C. 6. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C. yuan5805@gmail.com cleanclear0905@gmail.com. 7. Department of Nursing, Hungkuang University, Taichung, Taiwan, R.O.C.
Abstract
BACKGROUND/AIM: 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. 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 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. CONCLUSION: PYR demonstrated anti-tumour effects on NSCLC in vitro and in vivo, indicating its therapeutic potential against human NSCLC. Copyright
BACKGROUND/AIM: Pyrimethamine (PYR), an anti-malarial drug is known to inhibit various types of humancancer cells. The aim of this study was to investigate the anti-tumour effects of pyrimethamine (PYR) and its underlying molecular mechanisms using the humanNSCLC 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 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. CONCLUSION:PYR demonstrated anti-tumour effects on NSCLC in vitro and in vivo, indicating its therapeutic potential against humanNSCLC. Copyright
Authors: Richard E Kast; Alex Alfieri; Hazem I Assi; Terry C Burns; Ashraf M Elyamany; Maria Gonzalez-Cao; Georg Karpel-Massler; Christine Marosi; Michael E Salacz; Iacopo Sardi; Pieter Van Vlierberghe; Mohamed S Zaghloul; Marc-Eric Halatsch Journal: Cancers (Basel) Date: 2022-05-23 Impact factor: 6.575