Tag Archives: cell cycle

Biochemical aspects of the combined use of taxanes, irradiation and other antineoplastic agents for the treatment of anaplastic thyroid carcinoma

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

SI V. P. Komisarenko Institute of Endocrinology and Metabolism, NAMS of Ukraine, Kyiv;
e-mail: pushkarev.vm@gmail.com

The review summarizes the results of the cycle of own research and literature data on biochemical mechanisms of combined action of taxanes with γ-irradiation and other antineoplastic agents on one of the most aggressive types of human cancer – anaplastic thyroid carcinoma. Antagonistic interplay between taxanes and irradiation at the level of apoptotic mechanisms and regulators of the cell cycle are discussed. The effectiveness and prospects of using low concentrations of taxanes and low doses of fractional γ-irradiation are substantiated. Attention is paid to the role of inflammation and its key factor – NF-κB in the genesis of thyroid carcinomas and their treatment. Directions for further research are outlined.

Rhamnazin inhibits proliferation and induces apoptosis of human jurkat leukemia cells in vitro

А. А. Philchenkov, М. P. Zavelevych

R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology,
National Academy of Sciences of Ukraine, Kyiv;
e-mail: apoclub@i.ua

Antiproliferative and apoptogenic effects of rhamnazin, a dimethoxylated derivative of quercetin, were studied in human acute lymphoblastic leukemia Jurkat cells. The cytotoxicity and apoptogenic activity of rhamnazin in vitro are inferior to that of quercetin. The apoptogenic activity of rhamnazin is realized via mitochondrial pathway and associated with activation of caspase-9 and -3. The additive apoptogenic effect of rhamnazin and suboptimal doses of etoposide, a DNA topoisomerase II inhibitor, is demonstrated. Therefore, methylation of quercetin modifies its biological effects considerably.

Action of free and polymer carrier encapsulated doxorubicin towards HCT116 cells of human colorectal carcinoma

Yu. V. Senkiv1,2,4, P. Heffeter2, A. O. Riabtseva3, N. M. Boiko1,
O. S. Zaichenko3, N. Ye. Mitina3, W. Berger2, R. S. Stoika1

1Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
2Institute for Cancer Research, Medical University of Vienna, Austria;
3National University Lviv Polytechnic, Ukraine;
4Ivan Franko Lviv National University, Ukraine;
e-mail: stoika@cellbiol.lviv.ua

Development of novel nanoscale functionali­zed carriers is nowadays one of the most urgent problems in cancer treatment.  The aim of our study was to compare the antineoplastic effect of free doxorubicin and its complex with a nanoscale polymeric carrier towards HTC116 colorectal carcinoma cells. It was established that application of the complex of poly(5-tret-butylperoxy)-5-methyl-1-hexene-3-in-co-glycydyl metacrylat)-graft-polyethyleneglycol (poly(VEP-GMA-PEG)-graft-PEG), where VEP  – 5-tret-butylperoxy)-5-methyl-1-hexene-3-in; GMA – glycydyl metacrylat; graft-PEG – graft-polyethyleneglycol accordingly, functionali­zed with phosphatidylcholine for doxorubicin delivery increased 10 times the efficiency of cytotoxic action of this drug, as compared wich such efficiency in case of the action of free doxorubicin. The encapsulated form of doxorubicin caused more intensive cleavage of the reparation enzyme PARP and longer delay in G2/M cell cycle arrest, compared to such effects of free doxorubicin. The developed carrier itself is non-toxic to the used mammalian cells and does not cause impairment in their cell cycle. A deletion in both alleles of p53 gene did not affect the antineoplastic action of doxorubicin that was immobilized on the nanoscale carrier. Thus, p53-dependent signaling pathways are not involved in the cytotoxic action of doxorubicin-carrier complex. It is suggested that novel nanoscale polymeric carrier poly(VEP-GMA-PEG)-graft-PEG functionalized with phosphatidylcholine could be a promising carrier for targeted delivery of anticancer drugs.

Biochemical effects of combined action of γ-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 and Metabolism,
National Academy of Medical Sciences of Ukraine, Kyiv;
e-mail: pushkarev.vm@gmail.com

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.