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.