Effects of Cisplatin on Amino Acid Metabolism of Normal and Prostate Cancer Cells

Abstract

Background: Prostate cancer, which is a type of cancer affecting the male reproductive system, is the second most common type of cancer worldwide and constitutes 10% of all cancers in men. One of the primary treatment methods used in prostate cancer patients is chemotherapy. Cisplatin is a chemotherapy drug widely used in the treatment of many types of cancer, especially prostate cancer, and it acts by interfering with DNA replication and transcription processes. However, drug resistance against cisplatin in cancer cells and side effects on normal cells limit its use and reduce the treatment efficiency. Recently, resistance to cisplatin in cancer cells has been reported to be due to "metabolic reprogramming". Targeting metabolic processes therefore represents a potential new strategy to reverse cisplatin resistance. Materials and Methods: This study investigates the effects of cisplatin on amino acid metabolism of cancerous and normal prostate cells. In the study, 10 µM cisplatin was applied to prostate cancer cells (DU-145) and normal prostate cells (PNT-1A) in the medium and incubated for 24 hours. The free amino acid profile in the obtained cell lysate was analyzed by LC-MS/MS method. Data analysis was done with SPSS and metaboanalyst 5.0 program. Results: While the amount of arginine decreased in the PNT1A cells treated with cisplatin, the levels of taurine, phosphoethonalamine, ornithine and tryptophan were increased. It was determined that the amount of arginine, glycine and 2-Aminoheptandioic Acid increased, while sarcosine and beta alanine decreased in DU-145 cells when treated with cisplatin. Conclusions: As a result of the study, cisplatin has different effects on amino acid metabolism of normal and cancer cells, therefore, new studies by applying different amino acids in vitro may have positive effects in cancer treatment.