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.