Anticarcinogenic activity of Cl-Amidine on non-small cell lung cancer


Öğüten P. N., Engür Öztürk S., DİKMEN M.

Journal of Experimental and Clinical Medicine (Turkey), cilt.41, sa.1, ss.80-85, 2024 (Scopus) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 41 Sayı: 1
  • Basım Tarihi: 2024
  • Doi Numarası: 10.52142/omujecm.41.1.13
  • Dergi Adı: Journal of Experimental and Clinical Medicine (Turkey)
  • Derginin Tarandığı İndeksler: Scopus, Academic Search Premier
  • Sayfa Sayıları: ss.80-85
  • Anahtar Kelimeler: A549 cell line, Cl-amidine, lung cancer, peptidyl arginine deiminase inhibitor
  • Anadolu Üniversitesi Adresli: Evet

Özet

Peptidyl arginine deiminases (PADs) are enzymes that convert arginine to citrulline. They play a role in embryogenesis and cell signal transduction activities. However, it has been determined that excess or dysregulated PAD levels increase in many diseases and may be associated with diseases. Cl-amidine, used as a PAD inhibitor, has been shown to suppress PAD activity and reduce the severity of developing clinical pictures in animal experimental models such as rheumatoid arthritis and ulcerative colitis. Anti-proliferative activities have also been reported due to their cytotoxic effects on various cancer cell lines. In our study, the anti-carcinogenic activity of Cl-amidine was investigated in A549 human non-small cell lung cancer cells. The anti-proliferative effects of Cl-amide on A549 cells were determined by the WST-1 method. Apoptotic effects were analyzed on the flow cytometry device with Annexin V-PI, caspase-3 activation and mitochondrial membrane depolarization (JC-1) methods. It was determined by the WST-1 method that Cl-amidine had a significant anti-proliferative effect on A549, depending on time and concentration. The apoptotic effects analyzed by Annexin V-PI and JC-1 methods were found to be especially significant at the 48th hour. It has been determined that Cl-amidine, in particular, causes cells to undergo apoptosis by increasing mitochondrial depolarization. In addition, it was observed that Cl-amidine had a less cytotoxic effect on CCD-19Lu healthy lung cells than cisplatin, one of the existing treatment agents. This study shows that Cl-amidine has the potential to be an important chemotherapy agent in the lung cancer treatment, as it has a significant anti-proliferative and apoptotic effect on A549 cells, as well as being less cytotoxic when compared to existing cisplatin treatment on healthy lung cells. We believe that Cl-amidine will contribute to the discovery of new anti-cancer drugs by investigating it with single or combined agents.