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Evaluation of toxic effects of statins and their possible role in treatment of cancer

Yıl 2021, Cilt: 51 Sayı: 1, 154 - 160, 30.04.2021

Öz

Hydroxymethyl glutaryl CoA (HMG-CoA) reductase inhibitors (statins) are drugs that show hypolipidemic effect via inhibition of hydroxymethyl glutaryl CoA reductase (HMG CoA R), a rate-limiting step in the synthesis of cholesterol. The effects of statins, independent of lipid-lowering ones , are termed pleiotropic effects and these have gained importance in recent years. Potential anticancer effect, one of the pleotropic effects of statins, is remarkable. In this review we aim to summarize the possible use of statins in the treatment of cancer. Pleiotropic effects include antioxidant and antiinflammatory activities due to inhibition of new vessel formation in cancer cells, reduction of resistance to chemotherapeutic agents and inhibition of the production of reactive oxygen species (ROS) with the induction of apoptosis. The potential anticancer activity of statins against different tumor models is emphasized in vitro and in vivo conditions. For this reason, current efforts are directed to providing therapeutic benefits from statins in the treatment of cancer. This study shows that statins can be effective in preclinical models in advanced or recurrent metastatic diseases when administered alone or in combination with molecularly targeted agents. Future studies may shed further light on this topic.

Kaynakça

  • • Abdoli, N., Azarmi, Y., & Eghbal, M. A. (2015). Mitigation of statinsinduced cytotoxicity and mitochondrial dysfunction by L-carnitine in freshly-isolated rat hepatocytes. Research in Pharmaceutical Sciences, 10(2), 143–151.
  • • Ahmadi, M., Amiri, S., Pecic, S., Machaj, F., Rosik, J., Łos, M. J., ... & Shojaei, S. (2020). Pleiotropic effects of statins: a focus on cancer. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1866(12):165968.
  • • Al-Qatati, A., & Aliwaini, S. (2017). Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells. Oncology letters. 14(6):7993-7999.
  • • Baykara, O. (2016). Kanser tedavisinde güncel yaklaşımlar [Current modalities in treatment of cancer]. Balıkesir Sağlık Bilimleri Dergisi, 5(3), 154-165.
  • • Bedi, O., Dhawan, V., Sharma, P. L., & Kumar, P. (2016). Pleiotropic effects of statins: new therapeutic targets in drug design. Naunyn- Schmiedeberg’s archives of pharmacology, 389(7), 695-712.
  • • Berber, A. A., Celik, M., & Aksoy, H. (2014). Genotoxicity evaluation of HMG CoA reductase inhibitor rosuvastatin. Drug and chemical toxicology, 37(3), 316-321.
  • • Campos-Lara, M., & Mendoza-Espinoza, J. A. (2011). Cytotoxic evaluation of fluvastatin and rosuvastatin and effect of fluvastatin in the hela cell cycle. African Journal of Pharmacy and Pharmacology, 5(2), 189-193.
  • • Chae, Y. K., Yousaf, M., Malecek, M. K., Carneiro, B., Chandra, S., Kaplan, J., ... & Giles, F. (2015). Statins as anti-cancer therapy; Can we translate preclinical and epidemiologic data into clinical benefit?. Discovery medicine, 20(112), 413-427. Retrieved from https:// www.discoverymedicine.com
  • • Crescencio, M. E., Rodríguez, E., Páez, A., Masso, F. A., Montaño, L. F., & López-Marure, R. (2009). Statins inhibit the proliferation and induce cell death of human papilloma virus positive and negative cervical cancer cells. International journal of biomedical science: IJBS, 5(4), 411-420.
  • • Çetin, T., & Özgüneş, H. (2017). Statinlerin Toksikolojik Açıdan Değerlendirilmesi [Toxicological evaluation of statins]. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, (1), 18-28.
  • • Damrot, J., Nübel, T., Epe, B., Roos, W. P., Kaina, B., & Fritz, G. (2006). Lovastatin protects human endothelial cells from the genotoxic and cytotoxic effects of the anticancer drugs doxorubicin and etoposide. British journal of pharmacology, 149(8), 988-997.
  • • De Wolf, E., De Wolf, C., & Richardson, A. (2018). ABT‑737 and pictilisib synergistically enhance pitavastatin‑induced apoptosis in ovarian cancer cells. Oncology letters, 15(2), 1979-1984.
  • • Fan, Y., Sanyal, S., & Bruzzone, R. (2018). Breaking bad: how viruses subvert the cell cycle. Frontiers in cellular and infection microbiology, 8, 396. • Foster, I. (2008). Cancer: A cell cycle defect. Radiography, 14(2), 144-149.
  • • Gajski, G., & Garaj-Vrhovac, V. (2007). Application of cytogenetic endpoints and comet assay on human lymphocytes treated with atorvastatin in vitro. Journal of Environmental Science and Health, Part A, 43(1), 78-85.
  • • Gajski, G., Garaj-Vrhovac, V., & Oreščanin, V. (2008). Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: standard and Fpg-modified comet assay. Toxicology and applied pharmacology, 231(1), 85-93.
  • • Gauthaman, K., Fong, C. Y., & Bongso, A. (2009). Statins, stem cells, and cancer. Journal of cellular biochemistry, 106(6), 975-983.
  • • Gauthaman, K., Richards, M., Wong, J., & Bongso, A. (2007). Comparative evaluation of the effects of statins on human stem and cancer cells in vitro. Reproductive biomedicine online, 15(5), 566-581.
  • • Gruenbacher, G., & Thurnher, M. (2015). Mevalonate metabolism in cancer. Cancer letters, 356(2), 192-196.
  • • Gu, L., Saha, S. T., Thomas, J., & Kaur, M. (2019). Targeting cellular cholesterol for anticancer therapy. The FEBS journal, 286(21), 4192- 4208. • Internernet source 1. U.S. National Library of Medicine. (2020, October 16). Pitavastatin: Human Toxicity Excerpts. Retrieved from https://pubchem.ncbi.nlm.nih.gov/compound/5282452# section=Human-Toxicity-Excerpts
  • • Jiang, P., Mukthavaram, R., Chao, Y., Nomura, N., Bharati, I. S., Fogal, V., ... & Kapoor, S. (2014). In vitro and in vivo anticancer effects of mevalonate pathway modulation on human cancer cells. British journal of cancer, 111(8), 1562-1571. https://dx.doi.org/10.1038/bjc.2014.431
  • • Ho, C. K., & Walker, S. W. (2012). Statins and their interactions with other lipid-modifying medications: safety issues in the elderly. Therapeutic advances in drug safety, 3(1), 35-46. • Kato, S., Smalley, S., Sadarangani, A., Chen‐Lin, K., Oliva, B., Branes, J., ... & Cuello, M. (2010). Lipophilic but not hydrophilic statins selectively induce cell death in gynaecological cancers expressing high levels of HMGCoA reductase. Journal of cellular and molecular medicine, 14(5), 1180-1193. https://dx.doi.org/10.1111/j.1582- 4934.2009.00771.x
  • • Li, L. Z., Zhao, Z. M., Zhang, L., He, J., Zhang, T. F., Guo, J. B., ... & Peng, S. Q. (2019). Atorvastatin induces mitochondrial dysfunction and cell apoptosis in HepG2 cells via inhibition of the Nrf2 pathway. Journal of Applied Toxicology, 39(10), 1394-1404.
  • • Liu, A., Wu, Q., Guo, J., Ares, I., Rodríguez, J. L., Martínez-Larrañaga, M. R., ... & Martínez, M. A. (2019). Statins: Adverse reactions, oxidative stress and metabolic interactions. Pharmacology & therapeutics, 195, 54-84. https://dx.doi.org/10.1016/j. pharmthera.2018.10.004
  • • López-Aguilar, E., Sepúlveda-Vildósola, A. C., Betanzos-Cabrera, Y., Rocha-Moreno, Y. G., Gascón-Lastiri, G., Rivera-Márquez, H., ... & de la Cruz-Yañez, H. (2008). Phase II study of metronomic chemotherapy with thalidomide, carboplatin-vincristine-fluvastatin in the treatment of brain stem tumors in children. Archives of medical research, 39(7), 655-662. https://dx.doi.org/10.1016/j.arcmed. 2008.05.008
  • • Margaritis, M., Channon, K. M., & Antoniades, C. (2014). Statins as regulators of redox state in the vascular endothelium: beyond lipid lowering. Antioxidants & redox signaling, 20(8), 1198-1215. • Matusewicz, L., Meissner, J., Toporkiewicz, M., & Sikorski, A. F. (2015). The effect of statins on cancer cells. Tumor Biology, 36(7), 4889-4904.
  • • May, M. B., & Glode, A. (2016). Novel uses for lipid-lowering agents. Journal of the advanced practitioner in oncology, 7(2), 181-187.
  • • Osmak, M. (2012). Statins and cancer: current and future prospects. Cancer letters, 324(1), 1-12.
  • • Pisanti, S., Picardi, P., Ciaglia, E., D’Alessandro, A., & Bifulco, M. (2014). Novel prospects of statins as therapeutic agents in cancer. Pharmacological research, 88, 84-98.
  • • Pradelli, D., Soranna, D., Scotti, L., Zambon, A., Catapano, A., Mancia, G., ... & Corrao, G. (2013). Statins and primary liver cancer: a meta-analysis of observational studies. European journal of cancer prevention, 22(3), 229-234. https://dx.doi.org/10.1097/ CEJ.0b013e328358761a
  • • Qi, X. F., Kim, D. H., Yoon, Y. S., Kim, S. K., Cai, D. Q., Teng, Y. C., ... & Lee, K. J. (2010). Involvement of oxidative stress in simvastatin-induced apoptosis of murine CT26 colon carcinoma cells. Toxicology letters, 199(3), 277-287. https://dx.doi.org/10.1016/j.toxlet.2010.09.010
  • • Sabuncu, T., Sönmez, A., Bayram, F., Cesur, M., Aydoğdu, A., İzol Torun, A. N. (2016). Lipid metabolizma bozukluklari tani ve tedavi kilavuzu [Guide to diagnosis and treatment of lipid metabolism disorders]. Ankara, Turkey: Miki Matbaacılık.
  • • Sánchez, C. A., Rodriguez, E., Varela, E., Zapata, E., Paez, A., Massó, F. A., ... & Lopez-Marure, R. (2008). Statin-induced inhibition of MCF- 7 breast cancer cell proliferation is related to cell cycle arrest and apoptotic and necrotic cell death mediated by an enhanced oxidative stress. Cancer investigation, 26(7), 698-707. https://dx.doi. org/10.1080/07357900701874658
  • • Schafer, K. (1998). The cell cycle: a review. Vet Pathol, 35(6):461- 478.
  • • Schupp, N., Schmid, U., Heidland, A., & Stopper, H. (2008). Rosuvastatin protects against oxidative stress and DNA damage in vitro via upregulation of glutathione synthesis. Atherosclerosis, 199(2), 278-287.
  • • Shuhaili, M. F. R. M. A., Samsudin, I. N., Johnson Stanslas, S. H., & Thambiah, S. C. (2017). Effects of different types of statins on lipid profile: a perspective on Asians. International journal of endocrinology and metabolism, 15(2), e43319.
  • • Sodero, A. O., & Barrantes, F. J. (2020). Pleiotropic effects of statins on brain cells. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1862(9),183340.
  • • Stancu, C., & Sima, A. (2001). Statins: mechanism of action and effects. Journal of cellular and molecular medicine, 5(4), 378-387.
  • • Taylor-Harding, B., Orsulic, S., Karlan, B. Y., & Li, A. J. (2010). Fluvastatin and cisplatin demonstrate synergistic cytotoxicity in epithelial ovarian cancer cells. Gynecologic oncology, 119(3), 549-556.
  • • Tong, L., Chuang, C. C., Wu, S., & Zuo, L. (2015). Reactive oxygen species in redox cancer therapy. Cancer letters, 367(1), 18-25.
  • • Vermeulen, K., Berneman, Z. N., & Van Bockstaele, D. R. (2003). Cell cycle and apoptosis. Cell proliferation, 36(3), 165-175.
  • • Vermeulen, K., Van Bockstaele, D. R., & Berneman, Z. N. (2003). The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell proliferation, 36(3), 131-149.
  • • Villarino, N., Signaevskaia, L., van Niekerk, J., Medal, R., Kim, H., Lahmy, R., ... & Itkin-Ansari, P. (2017). A screen for inducers of bHLH activity identifies pitavastatin as a regulator of p21, Rb phosphorylation and E2F target gene expression in pancreatic cancer. Oncotarget, 8(32), 53154. https://dx.doi.org/10.18632/ oncotarget.18587
  • • Wong, W. W., Dimitroulakos, J., Minden, M. D., & Penn, L. Z. (2002). HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia, 16(4), 508-519.
  • • Yasui, Y., Suzuki, R., Miyamoto, S., Tsukamoto, T., Sugie, S., Kohno, H., & Tanaka, T. (2007). A lipophilic statin, pitavastatin, suppresses inflammation‐associated mouse colon carcinogenesis. International journal of cancer, 121(10), 2331-2339.
  • • You, H. Y., Zhang, W. J., Xie, X. M., Zheng, Z. H., Zhu, H. L., & Jiang, F. Z. (2016). Pitavastatin suppressed liver cancer cells in vitro and in vivo. OncoTargets and therapy, 9, 5383-5388.
  • • Zhang, W., Wu, J., Zhou, L., Xie, H. Y., & Zheng, S. S. (2010). Fluvastatin, a lipophilic statin, induces apoptosis in human hepatocellular carcinoma cells through mitochondria-operated pathway. Indian J Exp Biol, 48(12), 1167-1174.
  • • Zhang, Z. Y., Zheng, S. H., Yang, W. G., Yang, C., & Yuan, W. T. (2017). Targeting colon cancer stem cells with novel blood cholesterol drug pitavastatin. Eur Rev Med Pharmacol Sci, 21(6), 1226-1233.
Yıl 2021, Cilt: 51 Sayı: 1, 154 - 160, 30.04.2021

Öz

Kaynakça

  • • Abdoli, N., Azarmi, Y., & Eghbal, M. A. (2015). Mitigation of statinsinduced cytotoxicity and mitochondrial dysfunction by L-carnitine in freshly-isolated rat hepatocytes. Research in Pharmaceutical Sciences, 10(2), 143–151.
  • • Ahmadi, M., Amiri, S., Pecic, S., Machaj, F., Rosik, J., Łos, M. J., ... & Shojaei, S. (2020). Pleiotropic effects of statins: a focus on cancer. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1866(12):165968.
  • • Al-Qatati, A., & Aliwaini, S. (2017). Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells. Oncology letters. 14(6):7993-7999.
  • • Baykara, O. (2016). Kanser tedavisinde güncel yaklaşımlar [Current modalities in treatment of cancer]. Balıkesir Sağlık Bilimleri Dergisi, 5(3), 154-165.
  • • Bedi, O., Dhawan, V., Sharma, P. L., & Kumar, P. (2016). Pleiotropic effects of statins: new therapeutic targets in drug design. Naunyn- Schmiedeberg’s archives of pharmacology, 389(7), 695-712.
  • • Berber, A. A., Celik, M., & Aksoy, H. (2014). Genotoxicity evaluation of HMG CoA reductase inhibitor rosuvastatin. Drug and chemical toxicology, 37(3), 316-321.
  • • Campos-Lara, M., & Mendoza-Espinoza, J. A. (2011). Cytotoxic evaluation of fluvastatin and rosuvastatin and effect of fluvastatin in the hela cell cycle. African Journal of Pharmacy and Pharmacology, 5(2), 189-193.
  • • Chae, Y. K., Yousaf, M., Malecek, M. K., Carneiro, B., Chandra, S., Kaplan, J., ... & Giles, F. (2015). Statins as anti-cancer therapy; Can we translate preclinical and epidemiologic data into clinical benefit?. Discovery medicine, 20(112), 413-427. Retrieved from https:// www.discoverymedicine.com
  • • Crescencio, M. E., Rodríguez, E., Páez, A., Masso, F. A., Montaño, L. F., & López-Marure, R. (2009). Statins inhibit the proliferation and induce cell death of human papilloma virus positive and negative cervical cancer cells. International journal of biomedical science: IJBS, 5(4), 411-420.
  • • Çetin, T., & Özgüneş, H. (2017). Statinlerin Toksikolojik Açıdan Değerlendirilmesi [Toxicological evaluation of statins]. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, (1), 18-28.
  • • Damrot, J., Nübel, T., Epe, B., Roos, W. P., Kaina, B., & Fritz, G. (2006). Lovastatin protects human endothelial cells from the genotoxic and cytotoxic effects of the anticancer drugs doxorubicin and etoposide. British journal of pharmacology, 149(8), 988-997.
  • • De Wolf, E., De Wolf, C., & Richardson, A. (2018). ABT‑737 and pictilisib synergistically enhance pitavastatin‑induced apoptosis in ovarian cancer cells. Oncology letters, 15(2), 1979-1984.
  • • Fan, Y., Sanyal, S., & Bruzzone, R. (2018). Breaking bad: how viruses subvert the cell cycle. Frontiers in cellular and infection microbiology, 8, 396. • Foster, I. (2008). Cancer: A cell cycle defect. Radiography, 14(2), 144-149.
  • • Gajski, G., & Garaj-Vrhovac, V. (2007). Application of cytogenetic endpoints and comet assay on human lymphocytes treated with atorvastatin in vitro. Journal of Environmental Science and Health, Part A, 43(1), 78-85.
  • • Gajski, G., Garaj-Vrhovac, V., & Oreščanin, V. (2008). Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: standard and Fpg-modified comet assay. Toxicology and applied pharmacology, 231(1), 85-93.
  • • Gauthaman, K., Fong, C. Y., & Bongso, A. (2009). Statins, stem cells, and cancer. Journal of cellular biochemistry, 106(6), 975-983.
  • • Gauthaman, K., Richards, M., Wong, J., & Bongso, A. (2007). Comparative evaluation of the effects of statins on human stem and cancer cells in vitro. Reproductive biomedicine online, 15(5), 566-581.
  • • Gruenbacher, G., & Thurnher, M. (2015). Mevalonate metabolism in cancer. Cancer letters, 356(2), 192-196.
  • • Gu, L., Saha, S. T., Thomas, J., & Kaur, M. (2019). Targeting cellular cholesterol for anticancer therapy. The FEBS journal, 286(21), 4192- 4208. • Internernet source 1. U.S. National Library of Medicine. (2020, October 16). Pitavastatin: Human Toxicity Excerpts. Retrieved from https://pubchem.ncbi.nlm.nih.gov/compound/5282452# section=Human-Toxicity-Excerpts
  • • Jiang, P., Mukthavaram, R., Chao, Y., Nomura, N., Bharati, I. S., Fogal, V., ... & Kapoor, S. (2014). In vitro and in vivo anticancer effects of mevalonate pathway modulation on human cancer cells. British journal of cancer, 111(8), 1562-1571. https://dx.doi.org/10.1038/bjc.2014.431
  • • Ho, C. K., & Walker, S. W. (2012). Statins and their interactions with other lipid-modifying medications: safety issues in the elderly. Therapeutic advances in drug safety, 3(1), 35-46. • Kato, S., Smalley, S., Sadarangani, A., Chen‐Lin, K., Oliva, B., Branes, J., ... & Cuello, M. (2010). Lipophilic but not hydrophilic statins selectively induce cell death in gynaecological cancers expressing high levels of HMGCoA reductase. Journal of cellular and molecular medicine, 14(5), 1180-1193. https://dx.doi.org/10.1111/j.1582- 4934.2009.00771.x
  • • Li, L. Z., Zhao, Z. M., Zhang, L., He, J., Zhang, T. F., Guo, J. B., ... & Peng, S. Q. (2019). Atorvastatin induces mitochondrial dysfunction and cell apoptosis in HepG2 cells via inhibition of the Nrf2 pathway. Journal of Applied Toxicology, 39(10), 1394-1404.
  • • Liu, A., Wu, Q., Guo, J., Ares, I., Rodríguez, J. L., Martínez-Larrañaga, M. R., ... & Martínez, M. A. (2019). Statins: Adverse reactions, oxidative stress and metabolic interactions. Pharmacology & therapeutics, 195, 54-84. https://dx.doi.org/10.1016/j. pharmthera.2018.10.004
  • • López-Aguilar, E., Sepúlveda-Vildósola, A. C., Betanzos-Cabrera, Y., Rocha-Moreno, Y. G., Gascón-Lastiri, G., Rivera-Márquez, H., ... & de la Cruz-Yañez, H. (2008). Phase II study of metronomic chemotherapy with thalidomide, carboplatin-vincristine-fluvastatin in the treatment of brain stem tumors in children. Archives of medical research, 39(7), 655-662. https://dx.doi.org/10.1016/j.arcmed. 2008.05.008
  • • Margaritis, M., Channon, K. M., & Antoniades, C. (2014). Statins as regulators of redox state in the vascular endothelium: beyond lipid lowering. Antioxidants & redox signaling, 20(8), 1198-1215. • Matusewicz, L., Meissner, J., Toporkiewicz, M., & Sikorski, A. F. (2015). The effect of statins on cancer cells. Tumor Biology, 36(7), 4889-4904.
  • • May, M. B., & Glode, A. (2016). Novel uses for lipid-lowering agents. Journal of the advanced practitioner in oncology, 7(2), 181-187.
  • • Osmak, M. (2012). Statins and cancer: current and future prospects. Cancer letters, 324(1), 1-12.
  • • Pisanti, S., Picardi, P., Ciaglia, E., D’Alessandro, A., & Bifulco, M. (2014). Novel prospects of statins as therapeutic agents in cancer. Pharmacological research, 88, 84-98.
  • • Pradelli, D., Soranna, D., Scotti, L., Zambon, A., Catapano, A., Mancia, G., ... & Corrao, G. (2013). Statins and primary liver cancer: a meta-analysis of observational studies. European journal of cancer prevention, 22(3), 229-234. https://dx.doi.org/10.1097/ CEJ.0b013e328358761a
  • • Qi, X. F., Kim, D. H., Yoon, Y. S., Kim, S. K., Cai, D. Q., Teng, Y. C., ... & Lee, K. J. (2010). Involvement of oxidative stress in simvastatin-induced apoptosis of murine CT26 colon carcinoma cells. Toxicology letters, 199(3), 277-287. https://dx.doi.org/10.1016/j.toxlet.2010.09.010
  • • Sabuncu, T., Sönmez, A., Bayram, F., Cesur, M., Aydoğdu, A., İzol Torun, A. N. (2016). Lipid metabolizma bozukluklari tani ve tedavi kilavuzu [Guide to diagnosis and treatment of lipid metabolism disorders]. Ankara, Turkey: Miki Matbaacılık.
  • • Sánchez, C. A., Rodriguez, E., Varela, E., Zapata, E., Paez, A., Massó, F. A., ... & Lopez-Marure, R. (2008). Statin-induced inhibition of MCF- 7 breast cancer cell proliferation is related to cell cycle arrest and apoptotic and necrotic cell death mediated by an enhanced oxidative stress. Cancer investigation, 26(7), 698-707. https://dx.doi. org/10.1080/07357900701874658
  • • Schafer, K. (1998). The cell cycle: a review. Vet Pathol, 35(6):461- 478.
  • • Schupp, N., Schmid, U., Heidland, A., & Stopper, H. (2008). Rosuvastatin protects against oxidative stress and DNA damage in vitro via upregulation of glutathione synthesis. Atherosclerosis, 199(2), 278-287.
  • • Shuhaili, M. F. R. M. A., Samsudin, I. N., Johnson Stanslas, S. H., & Thambiah, S. C. (2017). Effects of different types of statins on lipid profile: a perspective on Asians. International journal of endocrinology and metabolism, 15(2), e43319.
  • • Sodero, A. O., & Barrantes, F. J. (2020). Pleiotropic effects of statins on brain cells. Biochimica et Biophysica Acta (BBA)-Biomembranes, 1862(9),183340.
  • • Stancu, C., & Sima, A. (2001). Statins: mechanism of action and effects. Journal of cellular and molecular medicine, 5(4), 378-387.
  • • Taylor-Harding, B., Orsulic, S., Karlan, B. Y., & Li, A. J. (2010). Fluvastatin and cisplatin demonstrate synergistic cytotoxicity in epithelial ovarian cancer cells. Gynecologic oncology, 119(3), 549-556.
  • • Tong, L., Chuang, C. C., Wu, S., & Zuo, L. (2015). Reactive oxygen species in redox cancer therapy. Cancer letters, 367(1), 18-25.
  • • Vermeulen, K., Berneman, Z. N., & Van Bockstaele, D. R. (2003). Cell cycle and apoptosis. Cell proliferation, 36(3), 165-175.
  • • Vermeulen, K., Van Bockstaele, D. R., & Berneman, Z. N. (2003). The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell proliferation, 36(3), 131-149.
  • • Villarino, N., Signaevskaia, L., van Niekerk, J., Medal, R., Kim, H., Lahmy, R., ... & Itkin-Ansari, P. (2017). A screen for inducers of bHLH activity identifies pitavastatin as a regulator of p21, Rb phosphorylation and E2F target gene expression in pancreatic cancer. Oncotarget, 8(32), 53154. https://dx.doi.org/10.18632/ oncotarget.18587
  • • Wong, W. W., Dimitroulakos, J., Minden, M. D., & Penn, L. Z. (2002). HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia, 16(4), 508-519.
  • • Yasui, Y., Suzuki, R., Miyamoto, S., Tsukamoto, T., Sugie, S., Kohno, H., & Tanaka, T. (2007). A lipophilic statin, pitavastatin, suppresses inflammation‐associated mouse colon carcinogenesis. International journal of cancer, 121(10), 2331-2339.
  • • You, H. Y., Zhang, W. J., Xie, X. M., Zheng, Z. H., Zhu, H. L., & Jiang, F. Z. (2016). Pitavastatin suppressed liver cancer cells in vitro and in vivo. OncoTargets and therapy, 9, 5383-5388.
  • • Zhang, W., Wu, J., Zhou, L., Xie, H. Y., & Zheng, S. S. (2010). Fluvastatin, a lipophilic statin, induces apoptosis in human hepatocellular carcinoma cells through mitochondria-operated pathway. Indian J Exp Biol, 48(12), 1167-1174.
  • • Zhang, Z. Y., Zheng, S. H., Yang, W. G., Yang, C., & Yuan, W. T. (2017). Targeting colon cancer stem cells with novel blood cholesterol drug pitavastatin. Eur Rev Med Pharmacol Sci, 21(6), 1226-1233.
Toplam 47 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri, Sağlık Kurumları Yönetimi
Bölüm Review
Yazarlar

Aysun Ökçesiz Bu kişi benim 0000-0001-9130-2853

Ülkü Ündeğer Bucurgat Bu kişi benim 0000-0002-6692-0366

Yayımlanma Tarihi 30 Nisan 2021
Gönderilme Tarihi 20 Ocak 2020
Yayımlandığı Sayı Yıl 2021 Cilt: 51 Sayı: 1

Kaynak Göster

APA Ökçesiz, A., & Ündeğer Bucurgat, Ü. (2021). Evaluation of toxic effects of statins and their possible role in treatment of cancer. İstanbul Journal of Pharmacy, 51(1), 154-160.
AMA Ökçesiz A, Ündeğer Bucurgat Ü. Evaluation of toxic effects of statins and their possible role in treatment of cancer. iujp. Nisan 2021;51(1):154-160.
Chicago Ökçesiz, Aysun, ve Ülkü Ündeğer Bucurgat. “Evaluation of Toxic Effects of Statins and Their Possible Role in Treatment of Cancer”. İstanbul Journal of Pharmacy 51, sy. 1 (Nisan 2021): 154-60.
EndNote Ökçesiz A, Ündeğer Bucurgat Ü (01 Nisan 2021) Evaluation of toxic effects of statins and their possible role in treatment of cancer. İstanbul Journal of Pharmacy 51 1 154–160.
IEEE A. Ökçesiz ve Ü. Ündeğer Bucurgat, “Evaluation of toxic effects of statins and their possible role in treatment of cancer”, iujp, c. 51, sy. 1, ss. 154–160, 2021.
ISNAD Ökçesiz, Aysun - Ündeğer Bucurgat, Ülkü. “Evaluation of Toxic Effects of Statins and Their Possible Role in Treatment of Cancer”. İstanbul Journal of Pharmacy 51/1 (Nisan 2021), 154-160.
JAMA Ökçesiz A, Ündeğer Bucurgat Ü. Evaluation of toxic effects of statins and their possible role in treatment of cancer. iujp. 2021;51:154–160.
MLA Ökçesiz, Aysun ve Ülkü Ündeğer Bucurgat. “Evaluation of Toxic Effects of Statins and Their Possible Role in Treatment of Cancer”. İstanbul Journal of Pharmacy, c. 51, sy. 1, 2021, ss. 154-60.
Vancouver Ökçesiz A, Ündeğer Bucurgat Ü. Evaluation of toxic effects of statins and their possible role in treatment of cancer. iujp. 2021;51(1):154-60.