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KMID : 0043320130360050619
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Archives of Pharmacal Research
2013 Volume.36 No. 5 p.619 ~ p.625
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Synergistic interaction of β-galactosyl-pyrrolidinyl diazeniumdiolate with cisplatin against three tumor cells
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Deng Lingling
Zhang Erli
Chen Chang
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Abstract
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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.
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KEYWORD
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Synergistic effect, β-Galactosyl-pyrrolidinyl diazeniumdiolate, Cisplatin, Anti-tumor activity
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