TMS (2,3′,4,5′-tetramethoxystilbene) is a specific and powerful CYP1B1 inhibitor, with an IC50 value of 6±2nmol/L[1]. TMS has been used in CYP1B1 enzyme activity studies and in screening and comparative studies of TMS analogues[2].
In vitro, TMS(0-20μmol/L) significantly inhibited 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-stimulated CYP1B1 protein and mRNA expression in a concentration-dependent manner in MCF-7, MCF-10A and HL-60 cells after 24 hours of incubation[3]. TMS (10μmol/L) treatment for 72 hours significantly inhibited the viability of MDA-MB-231 cells and induced cell apoptosis[4]. TMS (20μmol/L) treatment for 48 hours caused an increase in the level of cell cycle inhibitor p27kip1 and promoted the apoptosis of PC-3 prostate cancer cells[5].
In vivo, TMS, intraperitoneal injection of 300μg/kg every 3 days, normalized blood pressure in a rat model of hypertension, reduced CYP1B1 activity, inhibited cardiovascular and renal hypertrophy, and prevented increased vascular reactivity and endothelial dysfunction[6]. Daily treatment with TMS (600μg/kg; i.p.) for 6 weeks reduced the production of reactive oxygen species (ROS) and the increase in NADPH oxidase activity, and inhibited the increase in proinflammatory cytokines and catecholamines in spontaneously hypertensive rats (SHR), accompanied by the decreased plasma levels of inflammatory cytokines[7].
References:
[1]Kim S, Ko H, Park J E, et al. Design, synthesis, and discovery of novel trans-stilbene analogues as potent and selective human cytochrome P450 1B1 inhibitors[J]. Journal of medicinal chemistry, 2002, 45(1): 160-164.
[2]Chun Y J, Oh Y K, Kim B J, et al. Potent inhibition of human cytochrome P450 1B1 by tetramethoxystilbene[J]. Toxicology letters, 2009, 189(1): 84-89.
[3]Chun Y J, Lee S K, Kim M Y. Modulation of human cytochrome P450 1B1 expression by 2, 4, 3′, 5′-tetramethoxystilbene[J]. Drug metabolism and disposition, 2005, 33(12): 1771-1776.
[4]Chae Y S, Kim J G, Jung H J, et al. Anticancer effect of (E)-2-hydroxy-3′, 4, 5′-trimethoxystilbene on breast cancer cells by mitochondrial depolarization[J]. Cancer chemotherapy and pharmacology, 2011, 68: 349-358.
[5]Kim S W, Jung H K, Kim M Y. Induction of p27 kip1 by 2, 4, 3′, 5′-tetramethoxystilbene is regulated by protein phosphatase 2A-dependent Akt dephosphorylation in PC-3 prostate cancer cells[J]. Archives of pharmacal research, 2008, 31: 1187-1194.
[6]Sahan-Firat S, Jennings B L, Yaghini F A, et al. 2, 3′, 4, 5′-Tetramethoxystilbene prevents deoxycorticosterone-salt-induced hypertension: contribution of cytochrome P-450 1B1[J]. American Journal of Physiology-Heart and Circulatory Physiology, 2010, 299(6): H1891-H1901.
[7]Jennings B L, Montanez D E, May M E, et al. Cytochrome P450 1B1 contributes to increased blood pressure and cardiovascular and renal dysfunction in spontaneously hypertensive rats[J]. Cardiovascular drugs and therapy, 2014, 28: 145-161.
TMS（2,3',4,5'-tetramethoxystilbene）是一种特异性强效的CYP1B1抑制剂，IC50值为6±2nmol/L[1]。TMS已被用于CYP1B1酶活性研究以及TMS类似物的筛选与比对研究[2]。
在体外，在MCF-7、MCF-10A和HL-60细胞中，0-20μmol/L浓度的TMS孵育24小时后，能以浓度依赖方式显著抑制2,3,7,8-四氯二苯并二噁英（TCDD）刺激的CYP1B1蛋白及mRNA表达[3]。10μmol/L的TMS处理72小时可显著抑制MDA-MB-231细胞活力并诱导细胞凋亡[4]。当以20μmol/L浓度处理48小时后，TMS能提高细胞周期抑制蛋白p27kip1水平，并促进PC-3前列腺癌细胞的凋亡[5]。
在体内，高血压模型大鼠每3天腹腔注射300μg/kg剂量的TMS后，血压恢复正常水平，同时CYP1B1活性降低，心血管及肾脏肥大状态得到抑制，并预防了血管反应性增强和内皮功能障碍[6]。自发性高血压大鼠（SHR）连续6周每日腹腔注射600μg/kg的TMS后，不仅减少了活性氧（ROS）生成和NADPH氧化酶活性升高，还抑制了促炎细胞因子和儿茶酚胺的增加，同时血浆中炎症性细胞因子水平相应降低[7]。