Apoptotic and Cytotoxic Effects of Lisinopril and Amlodipine in Human Hepatocellular Carcinoma Cell Model

Abstract

Objective: This study aimed to evaluate the cytotoxic and apoptosis-inducing effects of lisinopril and amlodipine in a human hepatocellular carcinoma (Hep3B) cell model. Materials and Methods: The cytotoxic effects of Hep3B cells treated with lisinopril and amlodipine were assessed using the MTT assay. Cell viability was analyzed at 24, 48, and 72 hours, and IC₅₀ values were calculated. Apoptosis-related gene expression levels, including Bcl-2, Bcl-xL, Bax, and Bak, were determined using RT-qPCR. Statistical analyses were performed using one-way ANOVA, and differences with p<0.05 were considered significant. Results: Lisinopril reduced Hep3B cell viability in a concentration-dependent manner with an IC₅₀ value of 74.04 µg/ml (p<0.05). Similarly, amlodipine decreased cell viability with an IC₅₀ value of 38.04 µg/ml (p<0.05). Gene expression analysis revealed that lisinopril decreased the expression of the anti-apoptotic genes Bcl-2 and Bcl-xL while slightly increasing the pro-apoptotic genes Bax and Bak, whereas amlodipine strongly suppressed anti-apoptotic gene expression and enhanced pro-apoptotic gene expression (p<0.05). Conclusion: These findings suggest that lisinopril and amlodipine modulate apoptotic gene expression and proliferation in Hep3B cells, enhancing apoptosis. The observed cytotoxic and molecular effects indicate a potential anti-cancer activity, which may hold clinical relevance for hepatocellular carcinoma therapy.

Keywords

• Amlodipine
• Apoptosis
• Cell Proliferation
• Hepatocellular Carcinoma
• Lisinopril

Lisinopril ve Amlodipinin İnsan Hepatosellüler Karsinom Hücre Modelinde Apoptotik ve Sitotoksik Etkileri

Abstract

Amaç: Bu çalışmada, insan hepatosellüler karsinomu (Hep3B) hücre modelinde lisinopril ve amlodipinin sitotoksik etkileri ve apoptoz indüksiyonu üzerindeki etkilerinin değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: Lisinopril ve amlodipin ile muamele edilen Hep3B hücrelerinin sitotoksik etkileri, MTT testi kullanılarak değerlendirilmiştir. Hücre canlılığı 24, 48 ve 72. saatlerde analiz edilmiş ve IC₅₀ değerleri hesaplanmıştır. Apoptoz ile ilişkili gen ekspresyon düzeyleri, Bcl-2, Bcl-xL, Bax ve Bak belirteçleri kullanılarak RT-qPCR yöntemiyle değerlendirilmiştir. İstatistiksel analizler One-way ANOVA kullanılarak gerçekleştirilmiş ve p<0.05 olan farklar istatistiksel olarak anlamlı kabul edilmiştir. Bulgular: Lisinopril, Hep3B hücrelerinin viabilitesini konsantrasyon-bağımlı bir şekilde azaltmış ve IC₅₀: 74.04 µg/ml olarak sitotoksisite göstermiştir (p<0.05). Amlodipin uygulaması da benzer şekilde Hep3B hücrelerinin canlılığını konsantrasyon-bağımlı olarak azaltmış ve IC₅₀ değeri 38,04 µg/ml olarak bulunmuştur (p<0,05). Gen ekspresyon analizleri, lisinoprilin Bcl-2 ve Bcl-xL gibi anti-apoptotik genlerin ekspresyonunu azalttığını, Bax ve Bak gibi pro-apoptotik genlerin ise zamanla arttırdığını gösterirken, amlodipin anti-apoptotik genleri belirgin şekilde baskılayıp pro-apoptotik genleri güçlü şekilde artırdığını ortaya koymuştur (p<0.05). Sonuç: Bu bulgular, lisinopril ve amlodipinin Hep3B hücrelerinde apoptotik gen ekspresyonunu ve proliferasyonu modüle ederek apoptozu artırabileceğini göstermektedir. Gözlemlenen sitotoksik ve moleküler etkiler, potansiyel bir anti-kanser aktiviteye işaret etmekte olup hepatoselüler karsinom tedavisi açısından klinik açıdan önem taşıyabilirler.

Keywords

• Amlodipin
• Apoptozis
• Hücre Proliferasyonu
• Hepatosellüler Karsinom
• Lisinopril

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