Medical Laboratory Techniques Department, Al-maarif University College, Al-anbar-Ramadi, Iraq.
Veterinary medicine college, Al-Qasim green University, Al-Qasim, Iraq.
Int Immunopharmacol. 2022 Sep;110:109074. doi: 10.1016/j.intimp.2022.109074. Epub 2022 Jul 21.
Oxysterols are cholesterol metabolites generated in the liver and other peripheral tissues as a mechanism of removing excess cholesterol. Oxysterols have a wide range of biological functions, including the regulation of sphingolipid metabolism, platelet aggregation, and apoptosis. However, it has been found that metabolites derived from cholesterol play essential functions in cancer development and immunological suppression. In this regard, research indicates that 27-hydroxycholesterol (27-HC) might act as an estrogen, promoting the growth of estrogen receptor (ER) positive breast cancer cells. The capacity of cholesterol to dynamically modulate signaling molecules inside the membrane and particular metabolites serving as signaling molecules are two possible contributory processes. 27-HC is a significant metabolite produced mainly through the CYP27A1 (Cytochrome P450 27A1) enzyme. 27-HC maintains cholesterol balance biologically by promoting cholesterol efflux via the liver X receptor (LXR) and suppressing de novo cholesterol production through the Insulin-induced Genes (INSIGs). It has been demonstrated that 27-HC is able to function as a selective ER regulator. Moreover, enhanced 27-HC production is in favor of the growth of end-stage malignancies in the brain, thyroid organs, and colon, as shown in breast cancer, probably due to pro-survival and pro-inflammatory signaling induced by unbalanced levels of oxysterols. However, the actual role of 27-HC in cancer promotion and progression remains debatable, and many studies are warranted to be performed to unravel the precise function of these molecules. This review article will summarize the latest evidence on the deleterious or beneficial functions of 27-HC in various types of cancer, such as breast cancer, prostate cancer, colon cancer, gastric cancer, ovarian cancer, endometrial cancer, lung cancer, melanoma, glioblastoma, thyroid cancer, adrenocortical cancer, and hepatocellular carcinoma.
氧化固醇是肝脏和其他外周组织中产生的胆固醇代谢物，是去除多余胆固醇的一种机制。氧化固醇具有广泛的生物学功能，包括调节神经酰胺代谢、血小板聚集和细胞凋亡。然而，已经发现胆固醇衍生的代谢物在癌症发展和免疫抑制中起着重要作用。在这方面，研究表明 27-羟胆固醇（27-HC）可能作为一种雌激素，促进雌激素受体（ER）阳性乳腺癌细胞的生长。胆固醇动态调节膜内信号分子和特定代谢物作为信号分子的能力是两个可能的促成过程。27-HC 是一种主要通过 CYP27A1（细胞色素 P450 27A1）酶产生的重要代谢物。27-HC 通过肝脏 X 受体（LXR）促进胆固醇外排，并通过胰岛素诱导基因（INSIGs）抑制从头胆固醇生成，从而在生物学上维持胆固醇平衡。已经证明，27-HC 能够作为一种选择性 ER 调节剂发挥作用。此外，增强的 27-HC 产生有利于脑、甲状腺器官和结肠等终末期恶性肿瘤的生长，如在乳腺癌中所示，这可能是由于氧化固醇失衡引起的生存和促炎信号。然而，27-HC 在癌症促进和进展中的实际作用仍存在争议，需要进行更多的研究来揭示这些分子的精确功能。本文综述了最新的证据，表明 27-HC 在各种类型的癌症（如乳腺癌、前列腺癌、结肠癌、胃癌、卵巢癌、子宫内膜癌、肺癌、黑色素瘤、胶质母细胞瘤、甲状腺癌、肾上腺皮质癌和肝细胞癌）中具有有害或有益的功能。
