Cholesterol oxidase is an enzyme that catalyzes the oxidation of cholesterol and is used to detect and analyze the metabolic process of cholesterol[1]. Cholesterol oxidase can catalyze the oxidation of cholesterol, converting it into cholest-4-en-3-one and hydrogen peroxide, which helps maintain the balance of cholesterol levels within cells[2]. Cholesterol oxidase can be used to study the transport and metabolic mechanisms of cholesterol within cells, as well as the role of cholesterol in cell signaling[3]. Cholesterol oxidase also has anticancer properties and can slow the progression of cancer[4].
In vitro, treatment of cancer cell lines (HeLa, HepG2, MDA-MB-231, and BT474) with Cholesterol oxidase (0.093–0.327μM; 12h) significantly inhibits cell proliferation, promotes oxidative stress and apoptosis, induces cell cycle arrest in the G1 phase, and inhibits the cell cycle process[5]. After 24 hours of 4T1 cell treatment with Cholesterol oxidase (0.125U), Cholesterol oxidase significantly increased the mechanical tension and osmotic fragility of the plasma membrane by depleting cholesterol, leading to decreased tolerance to hypotonic shock and oxidative stress and inhibited cell migration[6].
In vivo, Cholesterol oxidase (50μg/mouse) was administered intraperitoneally once a week to 8- to 12-week-old male C3H/HeOuJ mice for 24 hours. Cholesterol oxidase significantly induced Th2 and pro-inflammatory immune responses in mice[7]. Cholesterol oxidase (3U/mouse; every 3 days) alone or in combination with doxorubicin (2mg/kg; daily) was administered intraperitoneally for 20 days to adult Swiss albino mice that had formed solid tumors after subcutaneous injection of Ehrlich ascites carcinoma (EAC) cells into the right hind limb. Cholesterol oxidase significantly inhibited the growth of EAC solid tumors, with a more pronounced effect when used in combination with doxorubicin[8].
References:
[1] Pollegioni L, Piubelli L, Molla G. Cholesterol oxidase: biotechnological applications. FEBS J. 2009 Dec;276(23):6857-70.
[2] Kreit J, Sampson NS. Cholesterol oxidase: physiological functions. FEBS J. 2009 Dec;276(23):6844-56.
[3] MacLachlan J, Wotherspoon AT, Ansell RO, et al. Cholesterol oxidase: sources, physical properties and analytical applications. J Steroid Biochem Mol Biol. 2000 Apr;72(5):169-95.
[4] Vrielink A, Ghisla S. Cholesterol oxidase: biochemistry and structural features. FEBS J. 2009 Dec;276(23):6826-43.
[5] Alapati K, Handanahal SS. Cytotoxic activity of cholesterol oxidase produced by Streptomyces sp. AKHSS against cancerous cell lines: mechanism of action in HeLa cells. World J Microbiol Biotechnol. 2021 Jul 21;37(8):141.
[6] Zhen W, Luo T, Wang Z, et al. Mechanoregulatory Cholesterol Oxidase-Functionalized Nanoscale Metal-Organic Framework Stimulates Pyroptosis and Reinvigorates T Cells. Small. 2023 Dec;19(52):e2305440.
[7] Szulc-Kielbik I, Brzostek A, Gatkowska J, et al. Determination of in vitro and in vivo immune response to recombinant cholesterol oxidase from Mycobacterium tuberculosis. Immunol Lett. 2020 Dec;228:103-111.
[8] El-Naggar NE, Soliman HM, El-Shweihy NM. Extracellular cholesterol oxidase production by Streptomyces aegyptia, in vitro anticancer activities against rhabdomyosarcoma, breast cancer cell-lines and in vivo apoptosis. Sci Rep. 2018 Feb 9;8(1):2706.
Cholesterol oxidase一种能够催化胆固醇氧化反应的酶，用于检测和分析胆固醇的代谢过程[1]。Cholesterol oxidase可以催化胆固醇的氧化反应，将胆固醇转化为胆甾-4-烯-3-酮和过氧化氢，有助于维持细胞内胆固醇水平的平衡[2]。Cholesterol oxidase可用于研究胆固醇在细胞内的运输和代谢机制，以及胆固醇在细胞信号传导中的作用[3]。Cholesterol oxidase还具有的抑癌作用，可减缓癌症发展[4]。
在体外，Cholesterol Oxidase（0.093–0.327μM；12h）处理癌细胞系（HeLa、HePG2、MDA-MB-231和Bt474），可显著抑制细胞增殖，促进氧化应激、细胞凋亡，诱导细胞周期阻滞于G1期，抑制细胞周期进程[5]。Cholesterol Oxidase（0.125U）处理4T1细胞24小时后，Cholesterol Oxidase通过消耗胆固醇显著增加了细胞膜的张力和渗透脆性，导致细胞对低渗冲击和氧化应激的耐受性降低，抑制了细胞迁移[6]。
在体内，Cholesterol Oxidase（50μg/只）每周一次腹腔注射，用于处理8至12周龄的C3H/HeOuJ雄性小鼠24小时。Cholesterol Oxidase显著诱导了小鼠体内Th2型和促炎性免疫反应[7]。Cholesterol Oxidase（3U/只；每3天一次）单独或与Doxorubicin（2mg/kg；每天一次）联合腹腔注射，连续注射20天，用于处理成年Swiss albino mice，这些小鼠在右后肢皮下注射Ehrlich ascites carcinoma（EAC）细胞后形成实体瘤。Cholesterol Oxidase显著抑制了EAC实体瘤的生长，与Doxorubicin联合使用时，抑制效果更为显[8]。