Differential effects of low and high doses of taxol in anaplastic thyroid cancer cells: possible implication of the PIN1 prolyl isomerase
To study the molecular mechanisms of dose-dependent effects of an anticancer drug, Taxol, on the cell cycle machinery and apoptosis-related proteins in thyroid anaplastic cancer cell lines ARO and KTC-2. Materials and Methods: Western blot analysis was used for the detection of various proteins and...
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| Date: | 2008 |
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| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
| Published: |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2008
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| Series: | Experimental Oncology |
| Subjects: | |
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| Journal Title: | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| Cite this: | Differential effects of low and high doses of taxol in anaplastic thyroid cancer cells: possible implication of the PIN1 prolyl isomerase / V.M. Pushkarev, D.V. Starenki, V.A. Saenko, V.V. Pushkarev, O.I. Kovzun, M.D. Tronko, I.D. Popadiuk, S. Yamashita // Experimental Oncology. — 2008. — Т. 30, № 3. — С. 190–194. — Бібліогр.: 32 назв. — англ. |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine| Summary: | To study the molecular mechanisms of dose-dependent effects of an anticancer drug, Taxol, on the cell cycle machinery and apoptosis-related proteins in thyroid anaplastic cancer cell lines ARO and KTC-2. Materials and Methods: Western blot analysis was used for the detection of various proteins and of their phosphorylated forms. Results: Low dose of Taxol that cause apoptosis (25 nM) enhanced Rb protein phosphorylation, decreased the expression of cyclin-dependent kinase inhibitors р27KIP1 and p21WAF1, and potentiated the accumulation of phosphorylated p53 and of the prolyl isomerase Pin1. High Taxol doses (100 and 1000 nM) that cause necrosis-like cell death drastically decreased Pin1 level in both cell lines. Conclusion: Low doses of Taxol promoted G1/S transition, thus exhibiting mitogen-like effect. Drug-induced Pin1 accumulation could probably facilitate this transition and in parallel contribute to apoptosis via the p53/p73-dependent mechanism. At higher doses of Taxol, there was a dramatic decrease of Pin1 levels which may be a reason for G2/M cell cycle arrest. |
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