Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh.
Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia.
Cancer Med. 2023 Feb;12(4):4367-4379. doi: 10.1002/cam4.5242. Epub 2022 Oct 7.
Estrogens have been implicated in the pathogenesis of various cancer types, including colorectal carcinoma (CRC). Estrogen receptors such as ERα and ERβ activate intracellular signaling cascades followed by binding to estrogen, resulting in important changes in cellular behaviors. The nuclear estrogen receptors, i.e. ERβ and ERα are responsible for the genomic actions of estrogens, whereas the other receptor, such as G protein-coupled estrogen receptor (GPER) regulates rapid non-genomic actions, which lead to secondary gene expression changes in cells. ERβ, the predominant estrogen receptor expressed in both normal and non-malignant colonic epithelium, has protective roles in colon carcinogenesis. ERβ may exert the anti-tumor effect through selective activation of pro-apoptotic signaling, increasing DNA repair, inhibiting expression of oncogenes, regulating cell cycle progression, and also by changing the micro-RNA pool and DNA-methylation. Thus, a better understanding of the underlying mechanisms of estrogen and its receptors in CRC pathogenesis could provide a new horizon for effective therapeutic development. Furthermore, using synthetic or natural compounds as ER agonists may induce estrogen-mediated anti-cancer activities against colon cancer. In this study, we report the most recent pre-clinical and experimental evidences related to ERs in CRC development. Also, we reviewed the actions of naturally occurring and synthetic compounds, which have a protective role against CRC development by acting as ER agonist.
雌激素与多种癌症类型的发病机制有关，包括结直肠癌（CRC）。雌激素受体（如 ERα 和 ERβ）激活细胞内信号级联反应，随后与雌激素结合，导致细胞行为发生重要变化。核雌激素受体，即 ERβ 和 ERα，负责雌激素的基因组作用，而其他受体，如 G 蛋白偶联雌激素受体（GPER）则调节快速非基因组作用，导致细胞中次级基因表达的变化。在正常和非恶性结肠上皮中均表达的主要雌激素受体 ERβ 在结肠癌变中具有保护作用。ERβ 可能通过选择性激活促凋亡信号、增加 DNA 修复、抑制癌基因表达、调节细胞周期进程，以及通过改变 microRNA 池和 DNA 甲基化来发挥抗肿瘤作用。因此，更好地了解雌激素及其受体在 CRC 发病机制中的潜在机制可能为有效的治疗开发提供新的前景。此外，使用合成或天然化合物作为 ER 激动剂可能会诱导雌激素介导的针对结肠癌的抗癌活性。在这项研究中，我们报告了与 CRC 发展中 ER 相关的最新临床前和实验证据。我们还回顾了天然存在和合成化合物的作用，这些化合物通过作为 ER 激动剂发挥作用，对 CRC 的发展具有保护作用。
