Investigation of natural diphtheria toxin as a potential anticancer agent in colorectal cancer: An in vitro analysis on HT-29 cells
Toxicon, cilt.262, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 262
- Basım Tarihi: 2025
- Doi Numarası: 10.1016/j.toxicon.2025.108386
- Dergi Adı: Toxicon
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, Environment Index, Metadex, Pollution Abstracts, Veterinary Science Database, Civil Engineering Abstracts
- Anahtar Kelimeler: Apoptosis, Cell cycle arrest, Colorectal cancer, Diphtheria toxin, DNA damage, HT-29
- Ankara Yıldırım Beyazıt Üniversitesi Adresli: Evet
Özet
Colorectal cancer (CRC) is the fourth most common cancer worldwide and the second leading cause of cancer-related deaths. The limited efficacy of conventional treatments underscores the need for alternative strategies. Among emerging candidates, diphtheria toxin (DT) has gained attention for its selective cytotoxicity, apoptosis induction, and inhibition of cancer cell proliferation with minimal harm to healthy cells. However, studies on DT's anticancer effects in CRC remain scarce. This study evaluated the cytotoxic and apoptotic effects of DT on HT-29 colorectal cancer cells. MTT assays confirmed DT's selective cytotoxicity, showing stronger effects on HT-29 cells than on normal Vero cells. Flow cytometry revealed DT-induced G1-phase cell cycle arrest. DNA fragmentation and qRT-PCR analyses demonstrated apoptosis activation, with upregulation of pro-apoptotic genes (Bax, FasL) and downregulation of Bcl-2. Additionally, qRT-PCR assessed key molecules in apoptosis, cell cycle regulation, and DNA damage response, including GADD45α, PARP1, p38α, p53, FoxO3a, and RbL2. Our findings suggest that DT inhibits HT-29 cell proliferation, induces apoptosis, and impacts DNA damage response, highlighting its potential as a therapeutic agent requiring further investigations.