title: 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.
authors.affiliation: College of Life Science and Technology, Beijing University of Chemical Technology, 301 Science & Tech Building, 15 North 3rd Ring East Road, Beijing, 100029, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Deng
authors.forename: Erli
authors.initials: E
authors.lastname: Zhang
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001391:Azo Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005690:Galactose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007763:Lac Operon / Q000235:genetics; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001391:Azo Compounds; D020030:Nitric Oxide Donors; C514571:beta-Gal-NONOate; D001616:beta-Galactosidase; D002945:Cisplatin; D005690:Galactose