Curcumin Potentiates The Ability of Sunitinib to Eliminate the VHL-lacking Renal Cancer Cells 786-O: Rapid Inhibition of Rb Phosphorylation as a Preamble to Cyclin D1 Inhibition

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


Volume 16, 12 Issues, 2016


Download PDF Flyer




Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

This journal supports open access

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 27th of 59 in Chemistry, Medicinal

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: 2.722
5 - Year: 2.849

Curcumin Potentiates The Ability of Sunitinib to Eliminate the VHL-lacking Renal Cancer Cells 786-O: Rapid Inhibition of Rb Phosphorylation as a Preamble to Cyclin D1 Inhibition



Anti-Cancer Agents in Medicinal Chemistry, 13(10): 1508-1513.

Author(s): Priya Ranjan Debata, Sultana Begum, Anita Mata, Oksana Genzer, Morton J. Kleiner, Probal Banerjee and Mario R Castellanos.

Affiliation: Department of Chemistry and the Center for Developmental Neuroscience, The City University of New York at The College of Staten Island, Staten Island, NY, 10314, USA.

Abstract

Curcumin, an important component of the culinary spice turmeric, has been shown to harbor anticancer properties against a wide range of cancer cells with minimal toxicity toward normal cells. Two general tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib are currently used in treating renal cancer. Though the use of these TKIs has significantly improved survival, both elicit distressing side effects, limiting their long-term use. We tested the activity of sunitinib and sorafenib to eliminate 786-O renal cancer cells and the efficacy of curcumin to enhance this process. A four-fold decrease in the IC50 of sunitinib, from 4.5 μM to 1.2 μM, was observed in the presence of 20-μM curcumin. However, curcumin did not potentiate the activity of sorafenib. The sunitinib-curcumin (SunC) combination sharply inhibited hyperphosphorylation of the tumor suppressor protein Rb within 8 hours of SunC treatment. Although the levels of cyclin D1 did not change in 8 hours, its expression was dramatically inhibited after 24 hours of SunC exposure. Since curcumin is known to inhibit the cyclin D1-dependent G1/S-phase kinase CDK4 and the cyclin B-dependent G2/M-phase kinase CDK1 that catalyze phosphorylation-mediated inactivation of Rb, our results indicate that SunC containing a lower dose of sunitinib would be effective in restoring the tumor suppressor activity of Rb, thereby truncating cell cycle and triggering cell death. Our results submit the possibility of using SunC as an effective antitumor formulation to reduce the dose and risk of adverse effects of sunitinib.

Keywords:

Curcumin, renal cancer, sorafenib, sunitinib.



Purchase Online Order Reprints Order Eprints Rights and Permissions




Article Details

Volume: 13
Issue Number: 10
First Page: 1508
Last Page: 1513
Page Count: 6
DOI: 10.2174/18715206113139990093
Price: $58
Advertisement

Related Journals




Webmaster Contact: urooj@benthamscience.org Copyright © 2016 Bentham Science