HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Synergistic interaction of β-galactosyl-pyrrolidinyl diazeniumdiolate with cisplatin against three tumor cells.

Abstract
Cisplatin is a platinum-based compound that is largely employed as an effective antitumor drug against a wide spectrum of solid neoplasms for many years. Despite of its initial therapeutic success, cisplatin often results in high incidence of chemoresistance and high-dose cytotoxicity. Consequently, considerable efforts in hopes of reducing the dose-dependent side effects of cisplatin while retaining, or even enhancing, its antitumor properties have been undertaken throughout the past three decades. Nitric oxide (NO) is a small lipophilic free radical gas possessing versatile biological functions, including antitumor activities. However, NO, of itself, is difficult to be used, because of its extreme instability and short half-life. Previously, we have reported a stable NO donor, β-galactosyl-pyrrolidinyl diazeniumdiolate (β-Gal-NONOate), which exerts tumor killing effects through site-specific intracellular release of exogenous NO. In this study, we further investigated the combined inhibitory effect of β-Gal-NONOate and cisplatin against C6/LacZ, 9L/LacZ, and HeLa/LacZ tumor cells. It was shown that, in combination with β-Gal-NONOate, the antitumor effects of cisplatin against these common tumor cell lines were increased in a dose-dependent manner. Furthermore, the combination of these chemicals resulted in a synergistic suppression on tumor growth, which was achieved under a much lower cisplatin dosage. Collectively, our findings indicate that β-Gal-NONOate can synergistically improve the antitumor effect of cisplatin, and may therefore reduce its side effects caused by high dose cisplatin monochemotherapies. Accordingly, β-Gal-NONOate is an important therapeutic assistant reagent with great potential of clinical applicability, and thus worth of continuous research in the coming future.
AuthorsLingling Deng, Erli Zhang, Chang Chen
JournalArchives of pharmacal research (Arch Pharm Res) Vol. 36 Issue 5 Pg. 619-25 (May 2013) ISSN: 1976-3786 [Electronic] Korea (South)
PMID23494564 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Azo Compounds
  • Nitric Oxide Donors
  • beta-Gal-NONOate
  • beta-Galactosidase
  • Cisplatin
  • Galactose
Topics
  • Animals
  • Antineoplastic Agents (administration & dosage, pharmacology)
  • Azo Compounds (administration & dosage, chemistry, pharmacology)
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Cisplatin (administration & dosage, pharmacology)
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Galactose (administration & dosage, analogs & derivatives, chemistry, pharmacology)
  • Humans
  • Lac Operon (genetics)
  • Nitric Oxide Donors (administration & dosage, pharmacology)
  • Rats
  • Transfection
  • beta-Galactosidase (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: