Kanser Hücre Hatlarına Karşı Epetraborolün Sitotoksik Aktivitesi

Abstract

Amaç: Antibiyotiklerin yeniden konumlandırılması, iyi karakterize edilmiş farmakoforların kanser hücrelerinde korunmuş zayıf noktaları hedeflemesine olanak tanıyan umut verici bir onkoloji stratejisidir. Bu çalışmada, benzoksaborol sınıfı bir lösil-tRNA sentetaz inhibitörü olan epetraborolün (EP) farklı kanser hücre tiplerine karşı sitotoksik potansiyelinin değerlendirilmesi amaçlanmıştır. Yöntemler: EP’nin sitotoksik etkileri; malign mezotelyoma (CARM-L12 TG3), osteosarkom (MG63) ve kolorektal karsinom (HT-29, SW-48 ve 2A3) olmak üzere beş farklı kanser hücre hattında incelenmiştir. Yetmiş iki saatlik maruziyet sonrası doz ve zamana bağlı yanıtları belirlemek amacıyla MTT hücre canlılığı testleri uygulanmıştır. Antibakteriyel aktivite, Escherichia coli’ye karşı minimum inhibitör konsantrasyonun (MİK) belirlenmesiyle doğrulanmıştır. Bulgular: EP, doz ve zamana bağlı olarak anlamlı sitotoksik aktivite göstermiştir. Bileşik, en yüksek etkinliği CARM-L12 TG3 (IC₅₀ = 0.408 ± 1.1 µg/mL) ve MG63 (IC₅₀ = 0.875 ± 1.6 µg/mL) hücre hatlarında sergilerken, kolorektal karsinom hücreleri daha düşük duyarlılık göstermiştir (IC₅₀ > 3 µg/mL). Antibakteriyel testler EP’nin biyolojik aktivitesini doğrulamış ve E. coli için MİK değeri 0.5 µg/mL olarak saptanmıştır. Sonuç: Epetraborol, özellikle mezotelyoma ve osteosarkom gibi mezenkimal kökenli kanserlere karşı güçlü bir sitotoksik potansiyel sergilemektedir. Elde edilen bulgular, EP’nin protein sentez mekanizmasına bağımlı maligniteleri hedefleyen onkolojik yeniden konumlandırma çalışmaları için umut verici bir aday olduğunu göstermektedir.

Keywords

• Epetraborol (AN3365)
• sitotoksisite
• kanser hücre hatları
• IC₅₀
• benzoksaborol
• MTT

CYTOTOXIC ACTIVITY OF EPETRABOROLE AGAINST CANCER CELL LINES

Abstract

Objective: Antibiotic repurposing represents a promising strategy in oncology, utilizing well-characterized pharmacophores to exploit conserved vulnerabilities in cancer cells. This study aimed to evaluate the cytotoxic potential of epetraborole (EP), a benzoxaborole-class leucyl-tRNA synthetase inhibitor, against various cancer cell types. Methods: The cytotoxic effects of EP were assessed in five cancer cell lines: malignant mesothelioma (CARM-L12 TG3), osteosarcoma (MG63), and colorectal carcinomas (HT-29, SW-48, and 2A3). MTT cell viability assays were conducted to determine dose- and time-dependent responses following 72-hour exposure. Antibacterial activity was verified by determining the minimum inhibitory concentration (MIC) against Escherichia coli. Results: EP exhibited significant cytotoxic activity in a dose- and time-dependent manner. The compound showed highest potency against CARM-L12 TG3 (IC50= 0.408 ± 1.1 µg/mL) and MG63 (IC₅₀ = 0.875 ± 1.6 µg/mL) cell lines, while colorectal carcinoma cells were less sensitive (IC50 > 3 µg/mL). Antibacterial testing confirmed EP’s bioactivity, with an MIC value of 0.5 μg/mL against E. coli. Conclusion: Epetraborole demonstrates strong cytotoxic potential, particularly against mesenchymal-derived cancers such as mesothelioma and osteosarcoma. These results suggest that EP is a promising candidate for repurposing in oncology, targeting malignancies dependent on protein synthesis machinery.

Keywords

• Epetraborole (AN3365)
• cytotoxicity
• cancer cell lines
• IC50
• benzoxaborole
• MTT

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