Department of Biotechnology, University of Rijeka, Rijeka, Croatia.
Anticancer Res. 2010 Oct;30(10):3987-94.
Several published studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) are promising anticancer agents. This study examined the in vitro effect of O-alkylated NSAID hydroxamic acid derivatives 3a-i on cell survival for a panel of human tumour cell lines, their cytotoxicity on normal human fibroblasts and their antiviral activity.
Established methods of cell viability testings, cell cycle analyses and Western blot assays were used.
O-Alkylated NSAID hydroxamic acid derivatives exerted poor antiviral activity butreduced the viability of the studied tumour cell lines in a concentration-dependent manner showing low cytotoxic effect on normal fibroblasts. Compounds 3a and 3i were shown to be potent inhibitors of the growth of MIA PaCa-2 cell line. They induced p53-independent S-phase arrest and triggered caspase 3-dependent apoptosis.
Two novel O-alkylated NSAID hydroxamic acid derivatives may be useful in the treatment of pancreatic cancer and should be further evaluated in vivo.
有几项已发表的研究表明，非甾体抗炎药（NSAIDs）是很有前途的抗癌药物。本研究考察了一系列 O-烷基化 NSAID 羟肟酸衍生物 3a-i 对人肿瘤细胞系细胞存活的体外影响、对正常人成纤维细胞的细胞毒性及其抗病毒活性。
采用了已建立的细胞活力检测、细胞周期分析和 Western blot 分析方法。
O-烷基化 NSAID 羟肟酸衍生物表现出较差的抗病毒活性，但以浓度依赖的方式降低了所研究的肿瘤细胞系的活力，对正常成纤维细胞的细胞毒性较低。化合物 3a 和 3i 被证明是 MIA PaCa-2 细胞系生长的有效抑制剂。它们诱导 p53 非依赖性 S 期停滞，并引发 caspase 3 依赖性细胞凋亡。
两种新型 O-烷基化 NSAID 羟肟酸衍生物可能对胰腺癌的治疗有用，应在体内进一步评估。
