Cisplatin’in Normal ve Prostat Kanseri Hücrelerinin Aminoasit Metabolizması Üzerine Etkileri

Öz

Amaç: Erkek üreme sistemini etkileyen bir kanser türü olan prostat kanseri, dünya genelinde en sık görülen ikinci kanser türü olup, erkeklerde tüm kanserlerin %10'unu oluşturmaktadır. Prostat kanseri hastalarında kullanılan birincil tedavi yöntemlerinden biri kemoterapidir. Cisplatin, prostat kanseri başta olmak üzere birçok kanser türünün tedavisinde yaygın olarak kullanılan bir kemoterapi ilacı olup, DNA replikasyonu ve transkripsiyon süreçlerine müdahale ederek etki gösterir. Fakat kanser hücrelerinde cisplatine karşı gelişen ilaç direnci ve normal hücreler üzerindeki yan etkiler bu ilacın kullanımı kısıtlayıp tedavi verimini azaltmaktadır. Son zamanlarda kanser hücrelerinde cisplatine karşı gelişen direncin “metabolik yeniden programlama” kaynaklı olduğu edilmiştir. Bu nedenle metabolik süreçleri hedeflemek, cisplatin direncini tersine çevirmek için potansiyel yeni bir stratejiyi temsil eder. Materyal ve Metod: Bu nedenle bu çalışma cisplatinin kanserli ve normal prostat hücrelerinin aminoasit metobolizması üzerindeki etkilerinin incelenmiştir. Çalışmada prostat kanseri hücresi (DU-145) ve normal prostat hücrelerine (PNT-1A) besi ortamında 10 µM cisplatin uygulanıp 24 saat inkübe edildi. Elde edilen hücre lizatındaki serbest aminoasit profili LC-MS/MS yöntemiyle incelendi. Verilerin analizi SPSS ve metaboanalist 5.0 programı ile yapıldı. Bulgular: Cisplatin uygulanan PNT1A hücrelerinde arginin miktarı azalırken, Taurin, fosfo etonalamin, ornitin ve triptofan seviyesinin arttığı gözlendi. Cisplatin uygulanan DU-145 hücrelerinde ise arginin, glisin ve 2-Aminoheptandioik Asit miktarının arttığı, sarkozin ve beta alanin ise azaldığı tespit edildi. Sonuç: Çalışma sonucunda cisplatin normal ve kanser hücrelerin aminoasit metabolizması üzerinde faklı etkiler gösterdiği, bu nedenle farklılık gösteren aminoasitlerin invitro ortamda uygulanarak yeni çalışmaların yapılması, kanser tedavisinde olumlu etkiler oluşturabilir.

Anahtar Kelimeler

• Prostat kanseri
• Cisplatin
• Aminoasit Metabolizması
• Metabolomik

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

Öz

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.

Anahtar Kelimeler

• Prostate cancer
• Cisplatin
• Amino acid Metabolism

Kaynakça

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