Deoxycholic acid (Cholanoic Acid) is a bile acid and a byproduct of intestinal metabolism that can activate the G protein-coupled bile acid receptor TGR5[1]. Deoxycholic acid can induce tyrosine phosphorylation and activate the receptor tyrosine kinase epidermal growth factor receptor in a ligand-independent manner[2]. Deoxycholic acid is the first drug that can be used to reduce submental fat[3].
In vitro, Deoxycholic acid (0-1000µM) treatment of AR42J cells for 24h inhibited cell proliferation in a dose- and time-dependent manner, induced cell apoptosis and necrosis, and significantly increased the activities of transcription factor 2 (ATF2), interferon-stimulated response element (ISRE), NKX-2.5, androgen receptor (AR), p53, and hypoxia-inducible factor-1 (HIF-1), and reduced the activities of peroxisome proliferator-activated receptor (PPAR) and activator protein 1 (AP1)[4]. Treatment of colon cancer cells (SW480 and LoVo) with Deoxycholic acid (5, 50µM) for 30min significantly increased tyrosine phosphorylation of β-catenin, leading to the loss of E-cadherin binding to β-catenin in the cells[5]. Treatment of gastric cancer cell MGC803 cells with Deoxycholic acid (100µM) for 2h enhanced cell survival and proliferation activity under bile acid stress[6].
In vivo, Deoxycholic acid added to drinking water at a concentration of 0.2% for 12 weeks in Apcmin/+ mice increased the incidence of intestinal tumors, increased intestinal permeability and induced low-grade inflammation[7].
References:
[1] Truong J K, Dawson P A. Bile acid metabolism[J]. Biochemistry of Lipids, Lipoproteins and Membranes, 2021: 395-428.
[2] Jean-Louis S, Akare S, Ali M A, et al. Deoxycholic acid induces intracellular signaling through membrane perturbations[J]. Journal of Biological Chemistry, 2006, 281(21): 14948-14960.
[3] Farina G A, Cherubini K, de Figueiredo M A Z, et al. Deoxycholic acid in the submental fat reduction: A review of properties, adverse effects, and complications[J]. Journal of Cosmetic Dermatology, 2020, 19(10): 2497-2504.
[4] Zhang G, Zhang J, Shang D, et al. Deoxycholic acid inhibited proliferation and induced apoptosis and necrosis by regulating the activity of transcription factors in rat pancreatic acinar cell line AR42J[J]. In Vitro Cellular & Developmental Biology-Animal, 2015, 51: 851-856.
[5] Pai R, Tarnawski A S, Tran T. Deoxycholic acid activates β-catenin signaling pathway and increases colon cell cancer growth and invasiveness[J]. Molecular biology of the cell, 2004, 15(5): 2156-2163.
[6] Wang X, Sun L, Wang X, et al. Acidified bile acids enhance tumor progression and telomerase activity of gastric cancer in mice dependent on c‐Myc expression[J]. Cancer Medicine, 2017, 6(4): 788-797.
[7] Liu L, Dong W, Wang S, et al. Deoxycholic acid disrupts the intestinal mucosal barrier and promotes intestinal tumorigenesis[J]. Food & function, 2018, 9(11): 5588-5597.
Deoxycholic acid (Cholanoic Acid)是一种胆汁酸，肠道代谢副产物，可以激活G 蛋白偶联胆汁酸受体TGR5[1]。Deoxycholic acid可以诱导酪氨酸磷酸化，并以不依赖配体的方式激活受体酪氨酸激酶表皮生长因子受体[2]。Deoxycholic acid是第一种可用于减少颏下脂肪的药物[3]。
在体外，Deoxycholic acid（0-1000µM）处理AR42J细胞24h，以剂量和时间依赖的方式抑制了细胞增殖，诱导了细胞凋亡和坏死，显著升高了转录因子2 （ATF2）、干扰素刺激反应元件（ISRE）、NKX-2.5、雄激素受体（AR）、p53、缺氧诱导因子-1（HIF-1）活性，降低了过氧化物酶体增殖激活受体（PPAR）、激活蛋白1（AP1）活性[4]。Deoxycholic acid（5、50µM）处理结肠癌细胞（SW480和LoVo）30min，显著增加β-连环蛋白的酪氨酸磷酸化，导致细胞中E-钙粘蛋白与β-连环蛋白结合的丧失[5]。Deoxycholic acid（100µM）处理胃癌细胞MGC803细胞2h，增强了细胞在胆汁酸应激下的存活和增殖活性[6]。
在体内，Deoxycholic acid以0.2%浓度添加到饮用水中喂养Apcmin/+小鼠12周，增加了肠道肿瘤的发生率，增加了肠道通透性并诱发低度炎症[7]。