Cancer chemoprevention is the use of synthetic, natural or biological agents to prevent or delay the development or progression of malignancies. Intriguingly, many phytochemicals with anti-inflammatory and anti-angiogenic effects, recently proposed as chemoprevention strategies, are inhibitors of Cytochrome P450 family 1B1 (CYP1B1), an enzyme overexpressed in a wide variety of tumors and associated with angiogenesis. In turn, pro-inflammatory cytokines were reported to boost CYP1B1 expression, suggesting a key role of CYP1B1 in a positive loop of inflammatory angiogenesis. Other well-known pro-tumorigenic activities of CYP1B1 rely on metabolic bioactivation of xenobiotics and steroid hormones into their carcinogenic derivatives. In contrast to initial in vitro observations, in vivo studies demonstrated a protecting role against cancer for the other CYP1 family members (CYP1A1 and CYP1A2), suggesting that the specificity of CYP1 family inhibitors should be carefully taken into account for developing potential chemoprevention strategies. Recent studies also proposed a role of CYP1B1 in multiple cell types found within the tumor microenvironment, including fibroblasts, endothelial and immune cells. Overall, our review of the current literature suggests a positive loop between inflammatory cytokines and CYP1B1, which in turn may play a key role in cancer angiogenesis, acting on both cancer cells and the tumor microenvironment. Strategies aiming at specific CYP1B1 inhibition in multiple cell types may translate into clinical chemoprevention and angioprevention approaches.

癌症化学预防方法是使用合成，天然或生物制剂预防或延迟恶性肿瘤的发生或发展。有趣的是，最近被提出作为化学预防策略的许多具有抗炎和抗血管生成作用的植物化学物质都是细胞色素P450家族1B1（CYP1B1）的抑制剂，该酶在多种肿瘤中过表达并与血管生成有关。反过来，据报道促炎性细胞因子可促进CYP1B1表达，提示CYP1B1在炎症性血管生成的阳性循环中起关键作用。CYP1B1的其他众所周知的促癌原活性还依赖于异生素和类固醇激素的代谢生物激活，使其成为致癌衍生物。与最初的体外观察相反，体内研究表明对其他CYP1家族成员（CYP1A1和CYP1A2）具有预防癌症的作用，提示在开发潜在的化学预防策略时应仔细考虑CYP1家族抑制剂的特异性。最近的研究还提出CYP1B1在肿瘤微环境中发现的多种细胞类型中的作用，包括成纤维细胞，内皮细胞和免疫细胞。总体而言，我们对当前文献的回顾表明，炎症细胞因子与CYP1B1之间存在正循环，而CYP1B1可能反过来在癌症血管生成中起着关键作用，对癌细胞和肿瘤微环境都起作用。针对多种细胞类型中特定CYP1B1抑制的策略可能会转化为临床化学预防和血管预防方法。