Biochemical effects of combined action of γ-irradiation and paclitaxel on anaplastic thyroid cancer cells
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 protei...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry
2013-02-01
|
| Series: | The Ukrainian Biochemical Journal |
| Subjects: | |
| Online Access: | http://ukrbiochemjournal.org/wp-content/uploads/2015/07/Pushkarev_1_13.pdf |
| _version_ | 1797428333292552192 |
|---|---|
| author | V. M. Pushkarev O. I. Kovzun V. V. Pushkarev M. D. Tronko |
| author_facet | V. M. Pushkarev O. I. Kovzun V. V. Pushkarev M. D. Tronko |
| author_sort | V. M. Pushkarev |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T08:56:32Z |
| format | Article |
| id | doaj.art-b8efa3fc2a5f4aa1b22ab32bcf979027 |
| institution | Directory Open Access Journal |
| issn | 2409-4943 2413-5003 |
| language | English |
| last_indexed | 2024-03-09T08:56:32Z |
| publishDate | 2013-02-01 |
| publisher | National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry |
| record_format | Article |
| series | The Ukrainian Biochemical Journal |
| spelling | doaj.art-b8efa3fc2a5f4aa1b22ab32bcf9790272023-12-02T12:56:56ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryThe Ukrainian Biochemical Journal2409-49432413-50032013-02-01851516110.15407/ubj85.01.051Biochemical effects of combined action of γ-irradiation and paclitaxel on anaplastic thyroid cancer cellsV. M. Pushkarev0O. I. Kovzun1V. V. Pushkarev2M. D. Tronko3State Institution V. P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, KyivState Institution V. P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, KyivState Institution V. P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, KyivState Institution V. P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine, KyivThe 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.http://ukrbiochemjournal.org/wp-content/uploads/2015/07/Pushkarev_1_13.pdfapoptosiscell cycleionizing radiationpaclitaxelthyroid cancer |
| spellingShingle | V. M. Pushkarev O. I. Kovzun V. V. Pushkarev M. D. Tronko Biochemical effects of combined action of γ-irradiation and paclitaxel on anaplastic thyroid cancer cells The Ukrainian Biochemical Journal apoptosis cell cycle ionizing radiation paclitaxel thyroid cancer |
| title | Biochemical effects of combined action of γ-irradiation and paclitaxel on anaplastic thyroid cancer cells |
| title_full | Biochemical effects of combined action of γ-irradiation and paclitaxel on anaplastic thyroid cancer cells |
| title_fullStr | Biochemical effects of combined action of γ-irradiation and paclitaxel on anaplastic thyroid cancer cells |
| title_full_unstemmed | Biochemical effects of combined action of γ-irradiation and paclitaxel on anaplastic thyroid cancer cells |
| title_short | Biochemical effects of combined action of γ-irradiation and paclitaxel on anaplastic thyroid cancer cells |
| title_sort | biochemical effects of combined action of γ irradiation and paclitaxel on anaplastic thyroid cancer cells |
| topic | apoptosis cell cycle ionizing radiation paclitaxel thyroid cancer |
| url | http://ukrbiochemjournal.org/wp-content/uploads/2015/07/Pushkarev_1_13.pdf |
| work_keys_str_mv | AT vmpushkarev biochemicaleffectsofcombinedactionofgirradiationandpaclitaxelonanaplasticthyroidcancercells AT oikovzun biochemicaleffectsofcombinedactionofgirradiationandpaclitaxelonanaplasticthyroidcancercells AT vvpushkarev biochemicaleffectsofcombinedactionofgirradiationandpaclitaxelonanaplasticthyroidcancercells AT mdtronko biochemicaleffectsofcombinedactionofgirradiationandpaclitaxelonanaplasticthyroidcancercells |