School of Pharmacy, College of Health Sciences, University of Zimbabwe, Mount Pleasant, Harare, Zimbabwe.
The African Academy of Sciences, P.O. Box 24916, Nairobi, Kenya.
Biomed Res Int. 2014;2014:752941. doi: 10.1155/2014/752941. Epub 2014 Jan 16.
Cancer is a major public health burden in both developed and developing countries. The quinone moiety has been shown to possess antitumor activity and several cancer drugs in clinical use contain this entity. The effect of isofuranonaphthoquinone isolated from Bulbine frutescens on Jurkat T cells was determined. Cells were exposed to the isofuranonaphthoquinone (IFNQ) at different concentrations. Significant antiproliferative effects were observed which were comparable to that of the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). A combination of IFNQ with BCNU produced synergistic effects which were observed after 72 hrs. It was also observed that combining IFNQ with reduced glutathione abolished the anticancer activity of the compound. It is, therefore, proposed that the isofuranonaphthoquinone may exert part of its effect by producing reactive oxygen species resulting in death of the cells as the effects of this compound were antagonized by reduced glutathione. An investigation on the effects of isofuranonaphthoquinone on glutathione transferase (GST) activity and drug efflux pumps showed that this compound exhibited inhibitory effects on both the GST and the drug efflux pumping activities. Thus, the isofuranonaphthoquinone showed cytotoxicity, works through inhibition of some cellular mechanisms, and could present a potential source of lead compounds for anticancer drug development.
癌症是发达国家和发展中国家的主要公共卫生负担。醌部分已被证明具有抗肿瘤活性,几种临床使用的癌症药物都含有这种物质。从 Bulbine frutescens 中分离出的异呋喃并萘醌对 Jurkat T 细胞的影响。将细胞暴露于不同浓度的异呋喃并萘醌(IFNQ)中。观察到明显的抗增殖作用,与抗癌药物 1,3-双(2-氯乙基)-1-亚硝脲(BCNU)相当。IFNQ 与 BCNU 联合使用产生协同作用,在 72 小时后观察到。还观察到,将 IFNQ 与还原型谷胱甘肽结合可消除该化合物的抗癌活性。因此,提出异呋喃并萘醌可能通过产生活性氧来发挥其部分作用,导致细胞死亡,因为该化合物的作用被还原型谷胱甘肽拮抗。对异呋喃并萘醌对谷胱甘肽转移酶(GST)活性和药物外排泵的影响的研究表明,该化合物对 GST 和药物外排泵活性均表现出抑制作用。因此,异呋喃并萘醌表现出细胞毒性,通过抑制某些细胞机制起作用,并可能为抗癌药物开发提供潜在的先导化合物来源。