Narayanan Narayanan K, Nargi Dominic, Attur Mukundan, Abramson Steven B, Narayanan Bhagavathi A
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
Anticancer Res. 2007 Jul-Aug;27(4B):2393-402.
Licofelone, a potent antiinflammatory agent has been reported to interfere with the cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) signaling pathways with few side-effects. However, the underlying mechanism of licofelone against human cancer is not understood.
Human and mouse prostate cancer cells were exposed to licofelone in a time- and dose-dependent manner. Cell growth/cell viability, apoptosis, and expression of COX-2 and 5-LOX at the gene and protein levels were investigated.
For the first time, it was demonstrated that licofelone inhibited prostate cancer cell growth and significantly down-regulated COX-2 and 5-LOX expression. A weak inhibitory effect on COX-1 protein was also observed.
Licofelone inhibited COX-2 and 5-LOX simultaneously and prevented overall cancer cell growth by enhancing apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. Validating the dual role of licofelone in animal models of prostate cancer is critical for promoting its use as a potential chemopreventive or therapeutic agent.
据报道,强力抗炎药利考非隆可干扰环氧合酶-2(COX-2)和5-脂氧合酶(5-LOX)信号通路,且副作用较少。然而,利考非隆抗人类癌症的潜在机制尚不清楚。
以时间和剂量依赖性方式将利考非隆作用于人和小鼠前列腺癌细胞。研究细胞生长/细胞活力、凋亡以及COX-2和5-LOX在基因和蛋白水平的表达。
首次证明利考非隆可抑制前列腺癌细胞生长,并显著下调COX-2和5-LOX的表达。还观察到对COX-1蛋白有微弱的抑制作用。
利考非隆可同时抑制COX-2和5-LOX,并通过增强雄激素依赖性和雄激素非依赖性前列腺癌细胞的凋亡来阻止癌细胞的整体生长。在前列腺癌动物模型中验证利考非隆的双重作用对于将其作为潜在的化学预防或治疗药物推广应用至关重要。