Ursodeoxycholic acid and its emerging role in attenuation of tumor growth in gastrointestinal malignancies
- Shailendra Kapoor
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I read with great interest the recent article by Tschirner et al. . Interestingly, recent data suggest that ursodeoxycholic acid (UDCA) may attenuate tumor growth in a number of gastrointestinal malignancies.
For instance, tauro-ursodeoxycholic acid when administered along with celecoxib attenuates proliferation and tumor growth in colonic adenomas . Interestingly, UDCA decreases the odds of advanced lesions in males only . Similarly, UDCA downregulates c-Myc expression . As a result, it attenuates tumor growth in colon carcinomas. CDK6 expression is also decreased secondary to UDCA administration. UDCA downregulates Cox-2 also, thus further inhibiting tumor growth. It also attenuates CCAAT/enhancer binding protein beta (C/EBPbeta) at the same time . It also effects p38 and Ras expression and thereby further modulates Cox-2 function. Recently, UDCA conjugates with glutamic acid have been developed that result in enhanced intraluminal delivery of UDCA inside th
- Tschirner A, von Haehling S, Palus S, Doehner W, Anker SD, Springer J. Ursodeoxycholic acid treatment in a rat model of cancer cachexia. J Cachexia Sarcopenia Muscle. 2012;3:31–6. doi:10.1007/s13539-011-0044-4. CrossRef
- van Heumen BW, Roelofs HM, Te Morsche RH, Marian B, Nagengast FM, Peters WH. Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells. Exp Cell Res. 2012;318:819–27. CrossRef
- Thompson PA, Wertheim BC, Roe DJ, et al. Gender modifies the effect of ursodeoxycholic acid in a randomized controlled trial in colorectal adenoma patients. Cancer Prev Res (Phila). 2009;2:1023–30. CrossRef
- Peiro-Jordan R, Krishna-Subramanian S, Hanski ML, Luscher-Firzlaff J, Zeitz M, Hanski C. The chemopreventive agent ursodeoxycholic acid inhibits proliferation of colon carcinoma cells by suppressing c-Myc expression. Eur J Cancer Prev. 2012;21:413–22. CrossRef
- Khare S, Mustafi R, Cerda S, et al. Ursodeoxycholic acid suppresses Cox-2 expression in colon cancer: roles of Ras, p38, and CCAAT/enhancer-binding protein. Nutr Cancer. 2008;60:389–400. CrossRef
- Asciutti S, Castellani D, Nardi E, et al. A new amino acid derivative of ursodeoxycholate, (N-L-glutamyl)-UDCA (UDCA-Glu), to selectively release UDCA in the colon. Anticancer Res. 2009;29:4971–9.
- Lim SC, Duong HQ, Parajuli KR, Han SI. Pro-apoptotic role of the MEK/ERK pathway in ursodeoxycholic acid-induced apoptosis in SNU601 gastric cancer cells. Oncol Rep. 2012;28:1429–34.
- Lim SC, Duong HQ, Choi JE, et al. Lipid raft-dependent death receptor 5 (DR5) expression and activation are critical for ursodeoxycholic acid-induced apoptosis in gastric cancer cells. Carcinogenesis. 2011;32:723–31. CrossRef
- Chung GE, Yoon JH, Lee JH, et al. Ursodeoxycholic acid-induced inhibition of DLC1 protein degradation leads to suppression of hepatocellular carcinoma cell growth. Oncol Rep. 2011;25:1739–46.
- Lim SC, Choi JE, Kang HS, Han SI. Ursodeoxycholic acid switches oxaliplatin-induced necrosis to apoptosis by inhibiting reactive oxygen species production and activating p53-caspase 8 pathway in HepG2 hepatocellular carcinoma. Int J Cancer. 2010;126:1582–95.
- Rudolph G, Kloeters-Plachky P, Rost D, Stiehl A. The incidence of cholangiocarcinoma in primary sclerosing cholangitis after long-time treatment with ursodeoxycholic acid. Eur J Gastroenterol Hepatol. 2007;19:487–91. CrossRef
- Ursodeoxycholic acid and its emerging role in attenuation of tumor growth in gastrointestinal malignancies
Journal of Cachexia, Sarcopenia and Muscle
Volume 3, Issue 4 , pp 277-278
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- 1. University of Illinois at Chicago, Chicago, IL, USA