Hill C U F Kelly, Saad Shaban E A, Britton Robert G, Gescher Andreas J, Sale Stewart, Brown Karen, Howells Lynne M
Chemoprevention Group, Department of Cancer Studies, RKCSB, Leicester Royal Infirmary, University of Leicester, Leicester, LE2 7LX, UK.
Cancer Chemother Pharmacol. 2015 Jul;76(1):179-85. doi: 10.1007/s00280-015-2771-2. Epub 2015 May 29.
TMFol (3',4',5'-trimethoxyflavonol) is a synthetic analogue of the naturally occurring flavonol fisetin and quercetin, which have been considered of potential usefulness in the management of prostate cancer. We investigated whether TMFol may have preclinical features superior to those of its two flavonol congeners.
The ability of the three flavonols to compromise prostate cancer cell survival was tested in four prostate cancer cell types 22Rv1, TRAMP C2, PC-3 and LNCaP. The effect of TMFol on prostate cancer development in vivo was investigated in nude mice bearing the 22Rv1 or TRAMP C2 tumours.
TMFol inhibited cell growth in vitro in all four prostate cancer cell types more potently than fisetin and quercetin. It also interfered with TRAMP C2 tumour development in vivo, while fisetin and quercetin at equivalent doses were without activity in this model. Likewise, TMFol slowed the growth of the 22Rv1 tumour in vivo. Efficacy in either model was accompanied by induction of apoptosis, although in vitro only TRAMP C2 cells, but not 22Rv1, underwent apoptosis when exposed to TMFol.
The results support the notion that among the three congeneric flavonols, quercetin, fisetin and TMFol, the latter may be the most suitable candidate agent for potential development in prostate cancer management.
TMFol(3',4',5'-三甲氧基黄酮醇)是天然存在的黄酮醇非瑟酮和槲皮素的合成类似物,它们在前列腺癌治疗中被认为具有潜在用途。我们研究了TMFol是否可能具有优于其两种黄酮醇同系物的临床前特征。
在四种前列腺癌细胞系22Rv1、TRAMP C2、PC-3和LNCaP中测试了这三种黄酮醇对前列腺癌细胞存活的影响。在携带22Rv1或TRAMP C2肿瘤的裸鼠中研究了TMFol对体内前列腺癌发展的影响。
TMFol在体外对所有四种前列腺癌细胞系的生长抑制作用比非瑟酮和槲皮素更强。它还在体内干扰了TRAMP C2肿瘤的发展,而同等剂量的非瑟酮和槲皮素在该模型中没有活性。同样,TMFol在体内减缓了22Rv1肿瘤的生长。两种模型中的疗效都伴随着细胞凋亡的诱导,尽管在体外只有TRAMP C2细胞,而不是22Rv1细胞,在暴露于TMFol时发生凋亡。
结果支持这样一种观点,即在三种同系黄酮醇槲皮素、非瑟酮和TMFol中,后者可能是前列腺癌治疗潜在开发中最合适的候选药物。