Anticancer Agent Ukrain and Bortezomib Combination is Synergistic in 4T1 Breast Cancer Cells

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 14, 10 Issues, 2014


Download PDF Flyer




Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 22nd of 58 in Chemistry, Medicinal
  • 85th of 202 in Oncology

Submit Abstracts Online Submit Manuscripts Online

Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 2.939
5 - Year: 3.37

Anticancer Agent Ukrain and Bortezomib Combination is Synergistic in 4T1 Breast Cancer Cells

Author(s): Bircan Savran, Azmi Yerlikaya, Elif Erdoğan and Osman Genç

Affiliation: Dumlupınar University, Faculty of Medicine, Department of Medical Biology, Kütahya, Turkey.

Abstract

The identification and in-depth understanding of intracellular signalling pathways led to the synthesis and discovery of many agents targeting cancer cells. In this study, we investigated for the first time the effect of anticancer agent ukrain as a single agent or in combination with cisplatin, etoposide, 5-fluorouracil, quercetin and bortezomib in 4T1 breast cancer and B16F10 melanoma cells. It was found that ukrain is cytotoxic and apoptotic in 4T1 breast carcinoma and B16F10 melanoma cells when given alone. The IC50 value of ukrain in 4T1 cells was found as 40 ± 6.8 μM and that in B16F10 cells as 76 ± 10 μM. It was then found that apoptosis can be induced in 4T1 breast cancer cells in a dose-dependent manner in response to ukrain treatment, based on DNA fragmentation evidence. The induction of apoptosis was corroborated by the analysis of cleavage products of caspase-3 in 4T1 cells using Western blot technique. When ukrain was tested in combination with cisplatin and etoposide, no significant enhancement of cytotoxicity was detected as compared with single agent treatments. Similarly, 5-fluorouracil and quercetin also did not potentiate the cytotoxic effects of ukrain in 4T1 cells. Finally, we examined the effect of various concentrations of ukrain in combination with 10 nM bortezomib in 4T1 cells. Determination of combination index values showed that bortezomib potentiated the effect of ukrain. And the combination was found to cause synergistic cell death. The lowest combination index detected was 0.57 which was obtained when the cells were treated with 10 nM bortezomib + 100 μM ukrain. Likewise, when cells were treated with different doses of bortezomib in the presence of 25 μM ukrain, synergism was similarly detected between the two drugs in a dose-dependent manner. Altogether, the results presented here suggest that the combination of ukrain + bortezomib may be further evaluated and tested in clinical settings.

Keywords: Apoptosis, bortezomib, cancer, synergism, ukrain.

Purchase Online Rights and Permissions

  
  



Article Details

Volume: 14
Issue Number: 3
First Page: 466
Last Page: 472
Page Count: 7
DOI: 10.2174/18715206113139990318
Advertisement


Webmaster Contact: urooj@benthamscience.org Copyright © 2014 Bentham Science