Comparative investigation of antitumoral effectiveness of Rho-kinase inhibitor Y-27632, pravastatin and atorvastatin in anaplastic thyroid cancer cell culture
Anaplastic thyroid cancer is an aggressive malignancy with a poor prognosis. In metastatic cases instead of treatment alternatives including surgery, radiotherapy, and chemotherapeutic regimens, targeted treatments should be sought for. Statins are 3-hidroxy-3 methylglutaryl-coenzyme A (HMG-CoA) red...
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| Format: | Article |
| Language: | English |
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Galenos Publishing House
2017-07-01
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| Series: | Journal of Oncological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452336417300456 |
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| author | Erdinc Nayir Selver Cor Zuhal Mert Altintas Kansu Buyukafsar Rukiye Nalan Tiftik Alper Ata Ali Arican |
| author_facet | Erdinc Nayir Selver Cor Zuhal Mert Altintas Kansu Buyukafsar Rukiye Nalan Tiftik Alper Ata Ali Arican |
| author_sort | Erdinc Nayir |
| collection | DOAJ |
| description | Anaplastic thyroid cancer is an aggressive malignancy with a poor prognosis. In metastatic cases instead of treatment alternatives including surgery, radiotherapy, and chemotherapeutic regimens, targeted treatments should be sought for.
Statins are 3-hidroxy-3 methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, and inhibit conversion of HMG-CoA into mevalonate. Inhibition of mevalonate pathway Ras prenylation, can also inhibit tumoral growth. Rho/Rho kinase pathway has an important role in tumoral proliferation, and metastasis in which activity of ROCK increases leading to tumoral invasion. Herein we investigated antitumoral effectiveness of two HMG-CoA reductase inhibitor statins namely pravastatin, and atorvastatin, and Rho-kinase inhibitor Y-27632 in anaplastic thyroid cancer cell cultures through suppression of cellular proliferation. Various concentrations of pravastatin (20, and 60 μM), and atorvastatin (10, and 30 μM), Y-27632 (10, and 30 μM), and their combinations including pravastatin -Y-27632 (20 μM + 10 μM; 60 μM + 30 μM), atorvastatin - Y-27632 (10 μM + 10 μM, and 30 μM + 30 μM) solutions were prepared. Anaplastic thyroid cancer cell culture media were treated with these more water-soluble drug solutions of pravastatin which induced lower dose-, and time-dependent decreases in cellular indices relative to more lipid-soluble atorvastatin which also markedly suppressed cellular proliferation. Y-27632 also decreased cell indices in a dose-, and time-dependent manner. Combination of Y-27632 with pravastatin, and atorvastatin did not demonstrate additive, synergic or antagonistic interactions.
HMG-CoA reductase, and also Rho-kinase inhibitors are promising treatment alternatives of anaplastic thyroid cancers. Further in vivo, and clinical studies are needed on this issue. |
| format | Article |
| id | doaj-art-c28311daa4ae43f09ec54a668310c8bb |
| institution | Kabale University |
| issn | 2452-3364 |
| language | English |
| publishDate | 2017-07-01 |
| publisher | Galenos Publishing House |
| record_format | Article |
| series | Journal of Oncological Sciences |
| spelling | doaj-art-c28311daa4ae43f09ec54a668310c8bb2025-08-20T03:57:39ZengGalenos Publishing HouseJournal of Oncological Sciences2452-33642017-07-0132626510.1016/j.jons.2017.05.005Comparative investigation of antitumoral effectiveness of Rho-kinase inhibitor Y-27632, pravastatin and atorvastatin in anaplastic thyroid cancer cell cultureErdinc Nayir0Selver Cor1Zuhal Mert Altintas2Kansu Buyukafsar3Rukiye Nalan Tiftik4Alper Ata5Ali Arican6Department of Medical Oncology, Kahramanmaras Necip Fazil City Hospital, Kahramanmaras, TurkeyDepartment of Internal Medicine, Kilis City Hospital, Kilis, TurkeyDepartment of Medical Biology and Genetics, Mersin University Faculty of Medicine, Mersin, TurkeyDepartment of Pharmacology, Mersin University Faculty of Medicine, Mersin, TurkeyDepartment of Pharmacology, Mersin University Faculty of Medicine, Mersin, TurkeyDepartment of Medical Oncology, Medicalpark Tarsus Hospital, Mersin, TurkeyDepartment of Medical Oncology, Acıbadem Hospital, Istanbul, TurkeyAnaplastic thyroid cancer is an aggressive malignancy with a poor prognosis. In metastatic cases instead of treatment alternatives including surgery, radiotherapy, and chemotherapeutic regimens, targeted treatments should be sought for. Statins are 3-hidroxy-3 methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, and inhibit conversion of HMG-CoA into mevalonate. Inhibition of mevalonate pathway Ras prenylation, can also inhibit tumoral growth. Rho/Rho kinase pathway has an important role in tumoral proliferation, and metastasis in which activity of ROCK increases leading to tumoral invasion. Herein we investigated antitumoral effectiveness of two HMG-CoA reductase inhibitor statins namely pravastatin, and atorvastatin, and Rho-kinase inhibitor Y-27632 in anaplastic thyroid cancer cell cultures through suppression of cellular proliferation. Various concentrations of pravastatin (20, and 60 μM), and atorvastatin (10, and 30 μM), Y-27632 (10, and 30 μM), and their combinations including pravastatin -Y-27632 (20 μM + 10 μM; 60 μM + 30 μM), atorvastatin - Y-27632 (10 μM + 10 μM, and 30 μM + 30 μM) solutions were prepared. Anaplastic thyroid cancer cell culture media were treated with these more water-soluble drug solutions of pravastatin which induced lower dose-, and time-dependent decreases in cellular indices relative to more lipid-soluble atorvastatin which also markedly suppressed cellular proliferation. Y-27632 also decreased cell indices in a dose-, and time-dependent manner. Combination of Y-27632 with pravastatin, and atorvastatin did not demonstrate additive, synergic or antagonistic interactions. HMG-CoA reductase, and also Rho-kinase inhibitors are promising treatment alternatives of anaplastic thyroid cancers. Further in vivo, and clinical studies are needed on this issue.http://www.sciencedirect.com/science/article/pii/S2452336417300456Anaplastic thyroid cancerROCKRho-kinase inhibitorStatin |
| spellingShingle | Erdinc Nayir Selver Cor Zuhal Mert Altintas Kansu Buyukafsar Rukiye Nalan Tiftik Alper Ata Ali Arican Comparative investigation of antitumoral effectiveness of Rho-kinase inhibitor Y-27632, pravastatin and atorvastatin in anaplastic thyroid cancer cell culture Journal of Oncological Sciences Anaplastic thyroid cancer ROCK Rho-kinase inhibitor Statin |
| title | Comparative investigation of antitumoral effectiveness of Rho-kinase inhibitor Y-27632, pravastatin and atorvastatin in anaplastic thyroid cancer cell culture |
| title_full | Comparative investigation of antitumoral effectiveness of Rho-kinase inhibitor Y-27632, pravastatin and atorvastatin in anaplastic thyroid cancer cell culture |
| title_fullStr | Comparative investigation of antitumoral effectiveness of Rho-kinase inhibitor Y-27632, pravastatin and atorvastatin in anaplastic thyroid cancer cell culture |
| title_full_unstemmed | Comparative investigation of antitumoral effectiveness of Rho-kinase inhibitor Y-27632, pravastatin and atorvastatin in anaplastic thyroid cancer cell culture |
| title_short | Comparative investigation of antitumoral effectiveness of Rho-kinase inhibitor Y-27632, pravastatin and atorvastatin in anaplastic thyroid cancer cell culture |
| title_sort | comparative investigation of antitumoral effectiveness of rho kinase inhibitor y 27632 pravastatin and atorvastatin in anaplastic thyroid cancer cell culture |
| topic | Anaplastic thyroid cancer ROCK Rho-kinase inhibitor Statin |
| url | http://www.sciencedirect.com/science/article/pii/S2452336417300456 |
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