Kodela Ravinder, Chattopadhyay Mitali, Kashfi Khosrow
Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, NY 10031, USA. Fax:(212) 650-7692; Tel: (212) 650-6641.
Medchemcomm. 2013;4(11). doi: 10.1039/C3MD00185G.
Nitric oxide- (NO) and hydrogen sulfide- (HS) releasing naproxen (NOSH-naproxen) and NO and HS-releasing sulindac (NOSH-sulindac) were synthesized and their cell growth inhibitory properties were evaluated in four different human cancer cell lines. These cell lines are of adenomatous (colon, pancreas), epithelial (breast), and lymphocytic (leukemia) origin. Using HT-29 human colon cancer cells, NOSH-naproxen and NOSH-sulindac increased apoptosis, and inhibited proliferation. NOSH-naproxen caused a G/G whereas NOSH-sulindac caused a G/M block in the cell cycle. Both compounds exhibited significant anti-inflammatory properties, using the carrageenan rat paw edema model. Reconstitution and structure-activity studies representing a fairly close approximation to the intact molecule showed that NOSH-naproxen was approximately 8000-fold more potent than the sum of its parts in inhibiting cell growth. Our data suggest that these compounds merit further investigation as potential anti-cancer agents.
合成了释放一氧化氮（NO）和硫化氢（HS）的萘普生（NOSH-萘普生）以及释放NO和HS的舒林酸（NOSH-舒林酸），并在四种不同的人类癌细胞系中评估了它们的细胞生长抑制特性。这些细胞系分别源自腺瘤（结肠、胰腺）、上皮（乳腺）和淋巴细胞（白血病）。使用HT-29人结肠癌细胞，NOSH-萘普生和NOSH-舒林酸可增加细胞凋亡并抑制增殖。NOSH-萘普生导致细胞周期停滞于G/G期，而NOSH-舒林酸导致细胞周期停滞于G/M期。在角叉菜胶诱导的大鼠足肿胀模型中，这两种化合物均表现出显著的抗炎特性。重构和结构-活性研究（相当接近完整分子）表明，在抑制细胞生长方面，NOSH-萘普生的效力比其各部分之和强约8000倍。我们的数据表明，这些化合物作为潜在的抗癌药物值得进一步研究。
