维康醇与维泰醇的抗肿瘤作用研究进展  

Research progress of natural compounds alternol/alteronol asanti-cancer agents

作　　者：刘旺 王衡 黄剑 李本义[1,2] LIU Wang;WANG Heng;HUANG Jian;LI Benyi(Department of Urology,University of Kansas Medical Center,Kansas,KS,66160,USA;Pathological Diagnosis and Research Center,Affiliated Hospital of Guangdong Medical University,Zhanjiang,Guangdong,524002,China)

机构地区：[1]堪萨斯大学医学院泌尿外科,美国堪萨斯州堪城66160 [2]广东医科大学附属医院临床病理诊断与研究中心,广东湛江524002

出　　处：《肿瘤药学》2021年第6期651-657,共7页Anti-Tumor Pharmacy

基　　金：国家自然科学基金项目(81572610);广东省扬帆紧缺拔尖人才项目(4YF16002G)。

摘　　要：维泰醇是从短叶红豆杉树皮的真菌突变株中提取并纯化的单体化合物,维康醇是其氧化物异构体。近期研究表明,二者均具有良好的特异性抗肿瘤活性,可干扰肿瘤细胞中多重信号通路的活性,调控细胞周期相关蛋白表达,引起细胞周期阻滞。维泰醇可特异性作用于黄嘌呤氧化酶,促进细胞内活性氧堆积,激活内源性凋亡通路,导致细胞死亡。蛋白质谱研究表明,维泰醇可特异性地与线粒体三羧酸循环中的4种酶蛋白结合,扰乱线粒体有氧呼吸功能和细胞能量代谢,减少ATP的产生,遏制体内肿瘤生长。维泰醇与维康醇均表现出抑制肿瘤细胞侵袭和迁移的能力,并可诱导肿瘤细胞分化。研究还指出,维泰醇具有选择性作用于肿瘤细胞的特性,对正常细胞无明显影响,目前在细胞水平和动物体内的实验均取得了良好的抗肿瘤效果,具有极大的研究价值和成药前景。Alternol is a monomeric compound extracted and purified from a mutant fungal strain of Taxus brevifolia bark.Alteronol is its oxide isomer.Recent studies have shown that both of them have potent and specific anti-tumor activity by interfering with multiple signal pathways in tumor cells,regulating the expressions of cell cycle-related proteins,and causing cell cycle arrest.Alternol specifically acts on xanthine oxidase,promotes the accumulation of reactive oxygen species in malignant cells,and activates intrinsic apoptotic pathway leading to cell death.Protein profiling studies discovered that alternol specifically binds to four enzymes which were involved in the mitochondrial tricarboxylic acid cycle,disrupting mitochondrial aerobic respiration and cellular energy metabolism,resulting in ATP reduction and xenograft tumor suppression in vivo.They also have shown the ability to inhibit tumor cell invasion and migration and to induce tumor cell differentiation.Most importantly,alternol has the property of selectively acting on tumor cells,no obvious effects on normal cells.Altogether,they possess potent anti-tumor effects at both cell culture models in vitro and xenograft models in vivo,representing a great research value and prospects as novel anti-cancer therapies.

关 键 词：维泰醇 维康醇 肿瘤 凋亡 细胞周期 氧自由基 

分 类 号：R979.1[医药卫生—药品]