Department of Biochemistry, Faculty of Pharmacy, Ankara University, Ankara, Turkey.
Department of Medical Biology, Faculty of Medicine, Ankara University, Ankara, Turkey.
Anticancer Agents Med Chem. 2018 Feb 7;17(14):1924-1930. doi: 10.2174/1871521409666170412122811.
Retinoids which are vitamin A (Retinol) derivatives have been suggested to mediate the inhibition of cancer cell growth and apoptosis. It has been reported that all trans retinoic acid (ATRA) exhibited suppressive effects on different types of leukemia including chronic myelogenous leukemia.
In the present study, we aim to find out the effects of 6 synthetic N-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydronaphthalene-2-yl)-carboxamide derivatives (compound 6-12) on cell viability and apoptotic pathways in K562 human chronic myelogenous leukemia cell line.
Cell viability and apoptosis were examined by spectrophotometric thiazolyl blue tetrazolium bromide (MTT) and caspase-3 assay, western blot, RT-PCR and flow cytometry.
Our results indicated that compound 6 (5-(1,2-Dithiolan-3-yl)-N-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydronaphthalen-2-yl)pentanamide), 8 (4-(3,4-Dimethoxyphenyl)-N-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydronaphthalen-2-yl)butanamide) and 11 (E-3-(4-Hydroxy-3-methoxyphenyl)-N-(3,5,5,8,8-pentamethyl- 5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide) exhibited apoptotic effects in K562 human chronic myelogenous leukemia cell line and induced caspase 3, PARP cleavage, Bax/Bcl-2 ratio, Bad and Bim gene expressions.
Some retinoid derivatives tested in this study induced apoptosis of K562 cells which suggest that these compounds may serve as potential agents in the treatment of chronic myelogenous leukemia.
视黄醇（维生素 A）衍生物类维 A 酸被认为可以抑制癌细胞生长和促进细胞凋亡。已有报道称，全反式维 A 酸（ATRA）对包括慢性髓性白血病在内的多种类型白血病具有抑制作用。
本研究旨在探讨 6 种合成 N-(3,5,5,8,8-五甲基-5,6,7,8-四氢萘-2-基）-羧酰胺衍生物（化合物 6-12）对 K562 人慢性髓性白血病细胞系细胞活力和凋亡途径的影响。
通过噻唑蓝溴化四唑（MTT）分光光度法和 caspase-3 测定法、western blot、RT-PCR 和流式细胞术检测细胞活力和细胞凋亡。
结果表明，化合物 6（5-（1,2-二硫戊环-3-基）-N-(3,5,5,8,8-五甲基-5,6,7,8-四氢萘-2-基）戊酰胺）、化合物 8（4-（3,4-二甲氧基苯基）-N-(3,5,5,8,8-五甲基-5,6,7,8-四氢萘-2-基）丁酰胺）和化合物 11（E-3-（4-羟基-3-甲氧基苯基）-N-(3,5,5,8,8-五甲基-5,6,7,8-四氢萘-2-基）丙烯酰胺）在 K562 人慢性髓性白血病细胞系中具有诱导细胞凋亡的作用，并诱导 caspase 3、PARP 切割、Bax/Bcl-2 比值、Bad 和 Bim 基因表达。
本研究中测试的一些维 A 酸衍生物诱导了 K562 细胞的凋亡，这表明这些化合物可能作为治疗慢性髓性白血病的潜在药物。
