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

Year 2026, Volume: 15 Issue: 1, 107 - 115, 28.02.2026
https://doi.org/10.53424/balikesirsbd.1794145
https://izlik.org/JA88TJ67JA

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.

Ethical Statement

As cell culture studies are performed strictly in vitro, they do not necessitate the use of human or animal subjects. Consequently, ethics committee approval is not required.

Supporting Institution

No funding was received for this study.

Project Number

non

Thanks

None.

References

  • Afsar, B., Afsar, R. E., Ertuglu, L. A., Kuwabara, M., Ortiz, A., Covic, A., Kanbay, M. (2021). Renin-angiotensin system and cancer: epidemiology, cell signaling, genetics and epigenetics. Clinical and Translational Oncology, 23(4), 682–696. https://doi.org/10.1007/s12094-020-02488-3
  • Akinyemiju, T., Abera, S., Ahmed, M., Alam, N., Alemayohu, M. A., Allen, C., Al-Raddadi, R., Alvis-Guzman, N., et al. (2017). The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the Global Burden of Disease Study 2015. JAMA Oncology, 3(12), 1683–1691. https://doi.org/10.1001/jamaoncol.2017.3055.
  • Almutlaq, M., Alamro, A. A., Alamri, H. S., Alghamdi, A. A., Barhoumi, T. (2021). The effect of local renin angiotensin system in the common types of cancer. Frontiers in Endocrinology, 12, 736361. https://doi.org/10.3389/fendo.2021.736361.
  • Alqudah, M. A. Y., Al-Samman, R., Azaizeh, M., Alzoubi, K. H. (2022). Amlodipine inhibits proliferation, invasion, and colony formation of breast cancer cells. Biomedical Reports, 16(6), 50. https://doi.org/10.3892/br.2022.1533.
  • Al-Rifaie, A., Khan, M. A., Ali, A., Dube, A. K., Gleeson, D., & Hoeroldt, B. (2020). Lisinopril-Induced Liver Injury: An Unusual Presentation and Literature Review. Eur J Case Rep Intern Med, 7(7), 001600. https://doi.org/10.12890/2020_001600.
  • Alvarenga, E. C., Fonseca, M. C., Carvalho, C. C., Florentino, R. M., França, A., Matias, E., Guimarães, P. B., Batista, C., Freire, V., Carmona, A. K., Pesquero, J. B., de Paula, A. M., Foureaux, G., Leite, M. F. (2016). Angiotensin converting enzyme regulates cell proliferation and migration. PLoS ONE, 11(12), e0165371. https://doi.org/10.1371/journal.pone.0165371.
  • Bao, J., Huang, B., Zou, L., Chen, S., Zhang, C., Zhang, Y., Chen, M., Wan, J. B., Su, H., Wang, Y., He, C. (2015). Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents. PLoS One, 10(9), e0139298. https://doi.org/10.1371/journal.pone.0139298.
  • Brunner-La Rocca, H. P., Vaddadi, G., Esler, M. D. (1999). Recent insight into therapy of congestive heart failure: focus on ACE inhibition and angiotensin-II antagonism. Journal of the American College of Cardiology, 33(5), 1163–1173. https://doi.org/10.1016/s0735-1097(99)00025-x.
  • Carlos-Escalante, J. A., de Jesús-Sánchez, M., Rivas-Castro, A., Pichardo-Rojas, P. S., Arce, C., & Wegman-Ostrosky, T. (2021). The Use of Antihypertensive Drugs as Coadjuvant Therapy in Cancer. Front Oncol, 11, 660943. https://doi.org/10.3389/fonc.2021.660943.
  • Chahine, J. J., Davis, S. S., Culfaci, S., Kallakury, B. V., Tuma, P. L. (2024). Chromosome 8q24 amplification associated with human hepatocellular carcinoma predicts MYC/ZEB1/MIZ1 transcriptional regulation. Scientific Reports, 14(1), 24488. https://doi.org/10.1038/s41598-024-75219-1
  • Chen, Y. J., Li, L. J., Tang, W. L., Song, J. Y., Qiu, R., Li, Q., Xue, H., Wright, J. M. (2018). First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension. Cochrane Database of Systematic Reviews, 11(11), CD008170. https://10.1002/14651858.CD008170.pub3.
  • Chuang, S. C., La Vecchia, C., Boffetta, P. (2009). Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Letters, 286(1), 9–14. https://10.1016/j.canlet.2008.10.040.
  • De Lange-Jacobs, P., Shaikh-Kader, A., Thomas, B., Nyakudya, T. T. (2020). An overview of the potential use of ethno-medicinal plants targeting the renin-angiotensin system in the treatment of hypertension. Molecules, 25(9), 2114. https://doi.org/10.3390/molecules25092114.
  • Duan, Y., Llorente, C., Lang, S., Brandl, K., Chu, H., Jiang, L., White, R. C., Clarke, T. H., et al. (2019). Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature, 575(7783), 505–511. https://doi.org/10.1038/s41586-019-1742-x.
  • Dziegielewska, B., Gray, L. S., Dziegielewski, J. (2014). T type calcium channels blockers as new tools in cancer therapies. Pflügers Archiv - European Journal of Physiology, 466, 801–810. https://10.1007/s00424-014-1444-z.
  • Fu, B., Dou, X., Zou, M., Lu, H., Wang, K., Liu, Q., Liu, Y., Wang, W., Jin, M., & Kong, D. (2022). Anticancer Effects of Amlodipine Alone or in Combination With Gefitinib in Non-Small Cell Lung Cancer. Front Pharmacol, 13, 902305. https://doi.org/10.3389/fphar.2022.902305.
  • GBD 2015 Mortality and Causes of Death Collaborators. (2016). Global, regional, and national life expectancy, all‐cause and cause‐specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet, 388(10053), 1459–1544. https://10.1016/S0140-6736(16)31012-1.
  • George, A. J., Allen, A., & Chand, A. L. (2017). Repurposing ARBs as Treatments for Breast Cancer. Aging (Albany NY), 9(5), 1357–1358. https://doi.org/10.18632/aging.101249
  • Hassani, B., Attar, Z., Firouzabadi, N. (2023). The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: foes versus allies. Cancer Cell International, 23(1), 254. https://doi.org/10.1186/s12935-023-03080-9.
  • Haznedaroglu, I. C., Malkan, U. Y. (2016). Local bone marrow renin-angiotensin system in the genesis of leukemia and other malignancies. European Review for Medical and Pharmacological Sciences, 20(19), 4089–4111.
  • Hicks, B. M., Filion, K. B., Yin, H., Sakr, L., Udell, J. A., Azoulay, L. (2018). Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study. BMJ, 363, k4209. https://doi.org/10.1136/bmj.k4209.
  • Hussain, M., Awan, F. R. (2018). Hypertension regulating angiotensin peptides in the pathobiology of cardiovascular disease. Clinical and Experimental Hypertension, 40(4), 344–352. https://doi.org/10.1080/10641963.2017.1377218.
  • Iheanacho, C. O., & Enechukwu, O. H. (2024). Role of antihypertensive medicines in prostate cancer: a systematic review. BMC Cancer, 24(1), 542. https://doi.org/10.1186/s12885-024-12218-5. Laurent, S. (2017). Antihipertansif İlaçlar. Pharmacol Res, 124, 116–125. https://doi.org/10.1016/j.phrs.2017.07.026.
  • Lee, Y., Kwon, Y. H. (2019). Regulation of apoptosis and autophagy by luteolin in human hepatocellular cancer Hep3B cells. Biochem Biophys Res Commun, 517(4), 617–622. https://doi.org/10.1016/j.bbrc.2019.07.073.
  • Li, C. I., Daling, J. R., Tang, M. T., Haugen, K. L., Porter, P. L., Malone, K. E. (2013). Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Internal Medicine, 173(17), 1629–1637. https://doi.org/10.1001/jamainternmed.2013.9071.
  • Luan, Z., Liu, B., Shi, L. (2019). Angiotensin II-induced micro RNA-21 culprit for non-small-cell lung adenocarcinoma. Drug Development Research, 80(8), 1031–1039. https://doi.org/10.1002/ddr.21597.
  • Maggioni, A. P. (2006). Efficacy of angiotensin receptor blockers in cardiovascular disease. Cardiovascular Drugs and Therapy, 20(4), 295–308. https://doi.org/10.1007/s10557-006-9799-9.
  • Mohammed, N. E., Messiha, B. A., & Abo-Saif, A. A. (2016). Effect of amlodipine, lisinopril and allopurinol on acetaminophen-induced hepatotoxicity in rats. Saudi Pharm J, 24(6), 635–644. https://doi.org/10.1016/j.jsps.2015.04.004.
  • Nehme, A., Zouein, F. A., Zayeri, Z. D., Zibara, K. (2019). An update on the tissue renin angiotensin system and its role in physiology and pathology. Journal of Cardiovascular Development and Disease, 6(2), 14. https://doi.org/10.3390/jcdd6020014.
  • Pasquier, E., André, N., Street, J., Chougule, A., Rekhi, B., Ghosh, J., et al. (2016). Effective Management of Advanced Angiosarcoma by the Synergistic Combination of Propranolol and Vinblastine-based Metronomic Chemotherapy: A Bench to Bedside Study. EBioMedicine, 6, 87–95. https://doi.org/10.1016/J.Ebiom.2016.02.026
  • Phan, N. N., Wang, C. Y., Chen, C. F., Sun, Z., Lai, M. D., Lin, Y. C. (2017). Voltage-gated calcium channels: novel targets for cancer therapy. Oncology Letters, 14(2), 2059–2074. https://doi.org/10.3892/ol.2017.6457.
  • Villanueva, A., Schwartz, M. E., Llovet, J. M. (2019). Liver cancer. Mount Sinai Expert Guides: Oncology, 89–100. https://doi.org/10.1002/9781119189596.ch8.
  • Wegman-Ostrosky, T., Soto-Reyes, E., Vidal-Millán, S., & Sánchez-Corona, J. (2015). The Renin-Angiotensin System Meets the Hallmarks of Cancer. JRAAS - J Renin-Angiotensin-Aldosterone Syst, 16(2), 227–233. https://doi.org/10.1177/1470320313496858.
  • Wong, B. S., Chiu, L. Y., Tu, D. G., Sheu, G. T., & Chan, T. T. (2020). Anticancer Effects of Antihypertensive L-Type Calcium Channel Blockers on Chemoresistant Lung Cancer Cells Via Autophagy and Apoptosis. Cancer Manag Res, 12, 1913–1927. https://doi.org/10.2147/CMAR.S228718.
  • Yet Kwong Horman, J., Patel, P., Schultz, M., & Kraschnewski, J. (2022). Amlodipine-Induced Liver Injury. Cureus, 14(3), e23441. https://doi.org/10.7759/cureus.23441.
  • Zhang, J., Dai, K., An, R., Wang, C., Zhou, X., Tian, Z., Liao, Z. (2025). Single Low-Dose Ionizing Radiation Transiently Enhances Rat RIN-m5F Cell Function via the ROS/p38 MAPK Pathway Without Inducing Cell Damage. Antioxidants, 14(2), 120. https://doi.org/10.3390/antiox14020120.

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

Year 2026, Volume: 15 Issue: 1, 107 - 115, 28.02.2026
https://doi.org/10.53424/balikesirsbd.1794145
https://izlik.org/JA88TJ67JA

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.

Ethical Statement

Hücre kültürü çalışmaları yalnızca in vitro koşullarda gerçekleştirildiğinden, insan veya hayvan deneklerin katılımını gerektirmez. Bu nedenle etik kurul onayı gerektirmemektedir.

Supporting Institution

Bu çalışma için destek alınmamıştır.

Project Number

non

Thanks

Yoktur.

References

  • Afsar, B., Afsar, R. E., Ertuglu, L. A., Kuwabara, M., Ortiz, A., Covic, A., Kanbay, M. (2021). Renin-angiotensin system and cancer: epidemiology, cell signaling, genetics and epigenetics. Clinical and Translational Oncology, 23(4), 682–696. https://doi.org/10.1007/s12094-020-02488-3
  • Akinyemiju, T., Abera, S., Ahmed, M., Alam, N., Alemayohu, M. A., Allen, C., Al-Raddadi, R., Alvis-Guzman, N., et al. (2017). The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the Global Burden of Disease Study 2015. JAMA Oncology, 3(12), 1683–1691. https://doi.org/10.1001/jamaoncol.2017.3055.
  • Almutlaq, M., Alamro, A. A., Alamri, H. S., Alghamdi, A. A., Barhoumi, T. (2021). The effect of local renin angiotensin system in the common types of cancer. Frontiers in Endocrinology, 12, 736361. https://doi.org/10.3389/fendo.2021.736361.
  • Alqudah, M. A. Y., Al-Samman, R., Azaizeh, M., Alzoubi, K. H. (2022). Amlodipine inhibits proliferation, invasion, and colony formation of breast cancer cells. Biomedical Reports, 16(6), 50. https://doi.org/10.3892/br.2022.1533.
  • Al-Rifaie, A., Khan, M. A., Ali, A., Dube, A. K., Gleeson, D., & Hoeroldt, B. (2020). Lisinopril-Induced Liver Injury: An Unusual Presentation and Literature Review. Eur J Case Rep Intern Med, 7(7), 001600. https://doi.org/10.12890/2020_001600.
  • Alvarenga, E. C., Fonseca, M. C., Carvalho, C. C., Florentino, R. M., França, A., Matias, E., Guimarães, P. B., Batista, C., Freire, V., Carmona, A. K., Pesquero, J. B., de Paula, A. M., Foureaux, G., Leite, M. F. (2016). Angiotensin converting enzyme regulates cell proliferation and migration. PLoS ONE, 11(12), e0165371. https://doi.org/10.1371/journal.pone.0165371.
  • Bao, J., Huang, B., Zou, L., Chen, S., Zhang, C., Zhang, Y., Chen, M., Wan, J. B., Su, H., Wang, Y., He, C. (2015). Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents. PLoS One, 10(9), e0139298. https://doi.org/10.1371/journal.pone.0139298.
  • Brunner-La Rocca, H. P., Vaddadi, G., Esler, M. D. (1999). Recent insight into therapy of congestive heart failure: focus on ACE inhibition and angiotensin-II antagonism. Journal of the American College of Cardiology, 33(5), 1163–1173. https://doi.org/10.1016/s0735-1097(99)00025-x.
  • Carlos-Escalante, J. A., de Jesús-Sánchez, M., Rivas-Castro, A., Pichardo-Rojas, P. S., Arce, C., & Wegman-Ostrosky, T. (2021). The Use of Antihypertensive Drugs as Coadjuvant Therapy in Cancer. Front Oncol, 11, 660943. https://doi.org/10.3389/fonc.2021.660943.
  • Chahine, J. J., Davis, S. S., Culfaci, S., Kallakury, B. V., Tuma, P. L. (2024). Chromosome 8q24 amplification associated with human hepatocellular carcinoma predicts MYC/ZEB1/MIZ1 transcriptional regulation. Scientific Reports, 14(1), 24488. https://doi.org/10.1038/s41598-024-75219-1
  • Chen, Y. J., Li, L. J., Tang, W. L., Song, J. Y., Qiu, R., Li, Q., Xue, H., Wright, J. M. (2018). First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension. Cochrane Database of Systematic Reviews, 11(11), CD008170. https://10.1002/14651858.CD008170.pub3.
  • Chuang, S. C., La Vecchia, C., Boffetta, P. (2009). Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Letters, 286(1), 9–14. https://10.1016/j.canlet.2008.10.040.
  • De Lange-Jacobs, P., Shaikh-Kader, A., Thomas, B., Nyakudya, T. T. (2020). An overview of the potential use of ethno-medicinal plants targeting the renin-angiotensin system in the treatment of hypertension. Molecules, 25(9), 2114. https://doi.org/10.3390/molecules25092114.
  • Duan, Y., Llorente, C., Lang, S., Brandl, K., Chu, H., Jiang, L., White, R. C., Clarke, T. H., et al. (2019). Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature, 575(7783), 505–511. https://doi.org/10.1038/s41586-019-1742-x.
  • Dziegielewska, B., Gray, L. S., Dziegielewski, J. (2014). T type calcium channels blockers as new tools in cancer therapies. Pflügers Archiv - European Journal of Physiology, 466, 801–810. https://10.1007/s00424-014-1444-z.
  • Fu, B., Dou, X., Zou, M., Lu, H., Wang, K., Liu, Q., Liu, Y., Wang, W., Jin, M., & Kong, D. (2022). Anticancer Effects of Amlodipine Alone or in Combination With Gefitinib in Non-Small Cell Lung Cancer. Front Pharmacol, 13, 902305. https://doi.org/10.3389/fphar.2022.902305.
  • GBD 2015 Mortality and Causes of Death Collaborators. (2016). Global, regional, and national life expectancy, all‐cause and cause‐specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet, 388(10053), 1459–1544. https://10.1016/S0140-6736(16)31012-1.
  • George, A. J., Allen, A., & Chand, A. L. (2017). Repurposing ARBs as Treatments for Breast Cancer. Aging (Albany NY), 9(5), 1357–1358. https://doi.org/10.18632/aging.101249
  • Hassani, B., Attar, Z., Firouzabadi, N. (2023). The renin-angiotensin-aldosterone system (RAAS) signaling pathways and cancer: foes versus allies. Cancer Cell International, 23(1), 254. https://doi.org/10.1186/s12935-023-03080-9.
  • Haznedaroglu, I. C., Malkan, U. Y. (2016). Local bone marrow renin-angiotensin system in the genesis of leukemia and other malignancies. European Review for Medical and Pharmacological Sciences, 20(19), 4089–4111.
  • Hicks, B. M., Filion, K. B., Yin, H., Sakr, L., Udell, J. A., Azoulay, L. (2018). Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study. BMJ, 363, k4209. https://doi.org/10.1136/bmj.k4209.
  • Hussain, M., Awan, F. R. (2018). Hypertension regulating angiotensin peptides in the pathobiology of cardiovascular disease. Clinical and Experimental Hypertension, 40(4), 344–352. https://doi.org/10.1080/10641963.2017.1377218.
  • Iheanacho, C. O., & Enechukwu, O. H. (2024). Role of antihypertensive medicines in prostate cancer: a systematic review. BMC Cancer, 24(1), 542. https://doi.org/10.1186/s12885-024-12218-5. Laurent, S. (2017). Antihipertansif İlaçlar. Pharmacol Res, 124, 116–125. https://doi.org/10.1016/j.phrs.2017.07.026.
  • Lee, Y., Kwon, Y. H. (2019). Regulation of apoptosis and autophagy by luteolin in human hepatocellular cancer Hep3B cells. Biochem Biophys Res Commun, 517(4), 617–622. https://doi.org/10.1016/j.bbrc.2019.07.073.
  • Li, C. I., Daling, J. R., Tang, M. T., Haugen, K. L., Porter, P. L., Malone, K. E. (2013). Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years. JAMA Internal Medicine, 173(17), 1629–1637. https://doi.org/10.1001/jamainternmed.2013.9071.
  • Luan, Z., Liu, B., Shi, L. (2019). Angiotensin II-induced micro RNA-21 culprit for non-small-cell lung adenocarcinoma. Drug Development Research, 80(8), 1031–1039. https://doi.org/10.1002/ddr.21597.
  • Maggioni, A. P. (2006). Efficacy of angiotensin receptor blockers in cardiovascular disease. Cardiovascular Drugs and Therapy, 20(4), 295–308. https://doi.org/10.1007/s10557-006-9799-9.
  • Mohammed, N. E., Messiha, B. A., & Abo-Saif, A. A. (2016). Effect of amlodipine, lisinopril and allopurinol on acetaminophen-induced hepatotoxicity in rats. Saudi Pharm J, 24(6), 635–644. https://doi.org/10.1016/j.jsps.2015.04.004.
  • Nehme, A., Zouein, F. A., Zayeri, Z. D., Zibara, K. (2019). An update on the tissue renin angiotensin system and its role in physiology and pathology. Journal of Cardiovascular Development and Disease, 6(2), 14. https://doi.org/10.3390/jcdd6020014.
  • Pasquier, E., André, N., Street, J., Chougule, A., Rekhi, B., Ghosh, J., et al. (2016). Effective Management of Advanced Angiosarcoma by the Synergistic Combination of Propranolol and Vinblastine-based Metronomic Chemotherapy: A Bench to Bedside Study. EBioMedicine, 6, 87–95. https://doi.org/10.1016/J.Ebiom.2016.02.026
  • Phan, N. N., Wang, C. Y., Chen, C. F., Sun, Z., Lai, M. D., Lin, Y. C. (2017). Voltage-gated calcium channels: novel targets for cancer therapy. Oncology Letters, 14(2), 2059–2074. https://doi.org/10.3892/ol.2017.6457.
  • Villanueva, A., Schwartz, M. E., Llovet, J. M. (2019). Liver cancer. Mount Sinai Expert Guides: Oncology, 89–100. https://doi.org/10.1002/9781119189596.ch8.
  • Wegman-Ostrosky, T., Soto-Reyes, E., Vidal-Millán, S., & Sánchez-Corona, J. (2015). The Renin-Angiotensin System Meets the Hallmarks of Cancer. JRAAS - J Renin-Angiotensin-Aldosterone Syst, 16(2), 227–233. https://doi.org/10.1177/1470320313496858.
  • Wong, B. S., Chiu, L. Y., Tu, D. G., Sheu, G. T., & Chan, T. T. (2020). Anticancer Effects of Antihypertensive L-Type Calcium Channel Blockers on Chemoresistant Lung Cancer Cells Via Autophagy and Apoptosis. Cancer Manag Res, 12, 1913–1927. https://doi.org/10.2147/CMAR.S228718.
  • Yet Kwong Horman, J., Patel, P., Schultz, M., & Kraschnewski, J. (2022). Amlodipine-Induced Liver Injury. Cureus, 14(3), e23441. https://doi.org/10.7759/cureus.23441.
  • Zhang, J., Dai, K., An, R., Wang, C., Zhou, X., Tian, Z., Liao, Z. (2025). Single Low-Dose Ionizing Radiation Transiently Enhances Rat RIN-m5F Cell Function via the ROS/p38 MAPK Pathway Without Inducing Cell Damage. Antioxidants, 14(2), 120. https://doi.org/10.3390/antiox14020120.
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Details

Primary Language English
Subjects Medical Pharmacology
Journal Section Research Article
Authors

Ayla Solmaz Avcıkurt 0000-0002-1521-7152

Sinem Gültekin Tosun 0009-0009-0899-3434

Project Number non
Submission Date September 30, 2025
Acceptance Date November 27, 2025
Publication Date February 28, 2026
DOI https://doi.org/10.53424/balikesirsbd.1794145
IZ https://izlik.org/JA88TJ67JA
Published in Issue Year 2026 Volume: 15 Issue: 1

Cite

APA Solmaz Avcıkurt, A., & Gültekin Tosun, S. (2026). Apoptotic and Cytotoxic Effects of Lisinopril and Amlodipine in Human Hepatocellular Carcinoma Cell Model. Balıkesir Sağlık Bilimleri Dergisi, 15(1), 107-115. https://doi.org/10.53424/balikesirsbd.1794145

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