title en

Journal archive > 2013 > N 1 January-February

BIOCHEMICAL EFFECTS OF COMBINED ACTION OF ?-IRRADIATION
AND PACLITAXEL ON ANAPLASTIC THYROID CANCER CELLS

V. M. Pushkarev, O. I. Kovzun, V. V. Pushkarev, M. D. Tronko

State Institution «V. P. Komisarenko Institute of Endocrinology & Metabolism»,
National Academy of Medical Sciences of Ukraine, Kyiv;
e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

The aim of the paper was to describe the biochemical effects of Paclitaxel (Ptx), ?-irradiation (IR) and their combination in undifferentiated thyroid cancer cells (ATC). IR activated common DNA damage-induced signaling and manifested certain mitogenic effect by inactivation of retinoblastoma protein (pRb). There was clear antagonism between Ptx and IR relative to cell cycle regulators – tumor suppressor p53, pRb, CHK2 and c-Abl as well as proapoptotic Bax expression, but combined action of both agents enhanced caspase-3 and, especially, caspase-8 activation. The Ptx at low (1-25 nM) concentrations caused noticeable radioprotective effect. Thus, in ATC cells the ionizing radiation and Ptx exhibited competitive effects upon phosphorylation of cell cycle controllers: p53, pRb, CHK2, cAbl and expression of Вах. At the same time, the combined effect of radiation and Ptx enhanced antiapoptotic Bcl-2 phosphorylation, caspases activation and survivin expression. The net effect of these events during the first 48-72 h of cells incubation can be considered as antiapoptotic - Ptx attenuated cytotoxic effect of IR.

Key words: paclitaxel, ionizing radiation, thyroid cancer, apoptosis, cell cycle.

The original article in English is available for download in PDF format.

© The Ukrainian Biochemical Journal