Biochemical effects of combined action of γ-irradiation and paclitaxel on anaplastic thyroid cancer cells

• Main Authors: V. M. Pushkarev, O. I. Kovzun, V. V. Pushkarev, M. D. Tronko
• Format: Article
• Language: English
• Published: National Academy of Sciences of Ukraine and Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine. 2013-02-01
• Series: Ukrainian Biochemical Journal
• Subjects: apoptosis; cell cycle; ionizing radiation; paclitaxel; thyroid cancer
• Online Access: http://ukrbiochemjournal.org/wp-content/uploads/2015/07/Pushkarev_1_13.pdf
• ISSN: 2409-4943; 2413-5003

The aim of the paper was to describe the biochemical effects of Paclitaxel (Ptx), γ-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.