Chemoprevention of Colon Carcinogenesis by Oleanolic Acid and Its Analog in Male F344 Rats and Modulation of COX-2 and Apoptosis in Human Colon HT-29 Cancer Cells
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
To assess the chemopreventive effect of oleanolic acid (ONA) and its synthetic analog 18α-olean-12-ene-3β-23,28-triol (OT) on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in F344 rats and understand anti-inflammatory properties and apoptosis effects in HT29 colon cancer cells and Raw 264.7 macrophage cell lines.
Five week-old male F344 rats were fed a control diet or experimental diets containing two doses of ONA (750 and 1,500 ppm) and OT (250 and 500 ppm). After 1 week, all animals were s.c. injected with AOM (15 mg/kg body weight, once weekly for 2 weeks). At 14 weeks of age, all rats were killed and colons were evaluated for ACF. Cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) expressions and apoptosis were assessed in cell lines exposed to OT using western blots and 4’,6-diamidino-2-phenylindole staining.
Administration of ONA and OT inhibited mean colonic ACF and multi-crypt AC/foci in a dose dependent manner (p < 0.001–0.0001). OT blocked the COX-2 expression induced by phorbol 12-myristate 13-acetate in a dose-dependent manner and induced apoptosis in HT-29 cancer cells, and suppressed iNOS activation in RAW264.7 macrophages.
- S. B. Mahato, and S. Sen. Advances in triterpenoid research 1990–1994. Phytochemistry. 44:1185–1236 (1997). CrossRef
- N. P. Sahu, S. B. Mahato, S. K. Sarkar, and G. Poddar. Triterpenoid saponins from Gymnema sylvestre. Phytochemistry. 41:1181–1185 (1996). CrossRef
- J. Liu. Pharmacology of oleanolic acid and ursolic acid. J. Ethnopharmacol. 49:57–68 (1995). CrossRef
- N. Suh, Y. Wang, T. Honda, G. W. Gribble, E. Dmitrovsky, W. F. Hickey, R. A. Maue, A. E. Place, D. M. Porter, M. J. Spinella, C. R. Williams, G. Wu, A. J. Dannenberg, K. C. Flanders, J. J. Letterio, D. J. Mangelsdorf, C. F. Nathan, L. Nguyen, W. W. Porter, R. F. Ren, N. S. Roche, K. Subbaramaiah, and M. B. Sporn. A novel synthetic oleanane triterpenoid, 2-cyno-3,12-dioxoolean-1,9-dien-28-oic acid, with potent differentiating antiproliferative and anti-inflammatory activity. Cancer Res. 59:336–341 (1999).
- B. J. Naveena, and C. V. Rao. Molecular markers and targets for colorectal cancer prevention. Acta Pharmacologica Sinica. 29:1–20 (2008).
- C. V. Rao. Nitric oxide signaling in colon cancer chemoprevention. Mutat. Res. 555:107–119 (2004).
- C. V. Rao, C. Indranie, B. Simi, P. T. Manning, J. R. Connor, and B. S. Reddy. Chemopreventive properties of a selective inducible nitric oxide synthase inhibitor in colon carcinogenesis, administered alone or in combination with celecoxib, a selective cyclooxygenase-2 inhibitor. Cancer Res. 62(1):165–70 (2002).
- M. Takahashi, K. Fukuda, T. Ohata, T. Sugimura, and K. Wakabayashi. Increased expression of inducible and endothelial constitutive nitric oxide synthases in rat colon tumors induced by azoxymethane. Cancer Res. 57:1233–1237 (1997).
- M. Tsujii, S. Kawano, S. Tsuji, H. Sawaoka, M. Hori, and R. Dubois. Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell. 93:705–716 (1998). CrossRef
- T. Hida, H. A. Yatabe, H. Muramatsu, K. Kozaki, S. Nakamura, M. Ogawa, M. Mitsudomi, S. Iwata, and S. Shibata. Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Res. 58:3761–3764 (1998).
- R. P. Bird. Role of aberrant crypt foci in understanding the pathogenesis of colon cancer. Cancer Lett. 93:55–71 (1995). CrossRef
- P. Greenwald, C. K. Clifford, and J. A. Milner. Diet and cancer prevention. Eur. J. Cancer. 37:948–965 (2001). CrossRef
- T. Fung, F. B. Hu, C. Fuchs, E. Giovannucci, D. J. Hunter, M. J. Stampfer, G. A. Colditz, and W. C. Willet. Major dietary patterns and the risk of colorectal cancer in women. Arch. Intern. Med. 163:309–314 (2003). CrossRef
- B. Chiu, B. Ji, Q. Dai, G. Gridley, J. K. Mclaughlin, Y. Gao, J. F. Fraumeni, and W. Chow. Dietary factors and risk of colon cancer in Shanghai, China. Cancer Epidemiol. Biomarkers Prev. 12:201–208 (2003).
- H. Nishino, A. Nishino, J. Takayasu, T. Hasegawa, A. Iwashima, K. Hirabayashi, S. Iwata, and S. Shibata. Inhibition of the tumor-promoting action of 12-O-tetradecanoylphorbol-13-acetate by some oleanane-type triterpenoid compounds. Cancer Res. 48:5210–5215 (1988).
- G. B. Singh, S. Singh, S. Bani, B. D. Gupta, and S. K. Banerjee. Anti-inflammatory activity of oleanolic acid in rats and mice. J. Pharm. Pharmacol. 44:456–458 (1992).
- M. T. Huang, C. T. Ho, Z. Y. Wang, T. Ferraro, Y. R. Lou, K. Stauber, W. Ma, C. Georgiadis, J. D. Laskin, and A. H. Conney. Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. Cancer Res. 54:701–708 (1994).
- C. Indranie, S. V. Malisetty, P. Jagan, L. E. S. Joel, V. E. Steele, and C. V. Rao. Chemoprevention of colon carcinogenesis by oleanolic acid and its analog in male F344rats and modulation of iNOS, COX-2 and apoptosis in human colon HT-29 cancer cells. AACR Proceeding. Abstract No. 819. 43:164–164 (2002).
- C. V. Rao, B. Simi, and B. S. Reddy. Inhibition by dietary curcumin of azoxymethane-induced ornithine decarboxylase, tyrosine protein kinase, arachidonic acid metabolism and aberrant crypt foci formation in the rat colon. Carcinogenesis. 14(11):2219–2225 (1993). CrossRef
- C. V. Rao, D. Desai, B. Simi, N. Kulkarni, S. Amin, and B. S. Reddy. Inhibitory effect of caffeic acid esters on azoxymethane-induced biochemical changes and aberrant crypt foci formation in rat colon. Cancer Res. 53:4182–4188 (1993).
- B. J. Naveena, C. Indranie, M. Altaf, V. E. Steele, and C. V. Rao. b-ionone inhibits colonic aberrant crypt foci in rats, suppresses cell growth and induces retinoid X receptor a in human colon cancer cells. Mol. Cancer Ther. 7(1):181–190 (2008). CrossRef
- R. Jayadev, M. R. P. Jagan, V. S. Malisetty, and C. V. Rao. Colon cancer preventive effects of Trigonella foenum graecum (fenugreek) seed and its constituent diosgenin in vivo and in vitro. Cancer Epidemiol. Biomarkers Prev. 13:1392–1398 (2004).
- T. Kawamoori, T. Tanaka, A. Hara, J. Yamahara, and H. Mori. Modifying effects of naturally occurring products on the development of colonic aberrant crypt foci by azoxymethane in F344 rats. Cancer Res. 55:1277–1282 (1995).
- H. Ohigashi, H. Takamura, K. Koshimizu, H. Tokuda, and Y. Ito. Search for possible antitumor promoters by inhibition of n-O-tetradecanoylphorbol-B-acetate induced Epstein–Barr virus activation: ursolic acid and oleanolic acid from an anti-inflammatory Chinese medicinal plant, Glechoma hederaceae L. Cancer Lett. JO:143–151 (1986). CrossRef
- N. Yoshimi, A. Wang, Y. Morishita, T. Tanaka, S. Sugie, K. Kawai, J. Yamahara, and H. Mori. Modifying effects of fungal and herb metabolites on azoxymethane-induced intestinal carcinogenesis in rats. Jpn. J. Cancer Res. 83:1273–1278 (1992).
- Z. Ovesna, A. Vachalkova, K. Horvathova, and D. Tothova. Pentacyclic triterpenic acids: New chemoprotective compounds. Neoplasma. 51:327–333 (2004).
- Gu. Yongchuan, G. Wang, G. Pan, J. P. Fawcett, A. Jiye, and S. Jianguo. Transport and bioavailability studies of astragaloside IV, an active ingredient in radix astragali. Basic Clin. Pharmacol. Toxicol. 95(6):295–298 (2004). CrossRef
- Y. Motoo, and N. Sawabu. Antitumor effects of saikosaponins, baicalin and baicalein on human hepatoma cell lines. Cancer Lett. 86:91–95 (1994). CrossRef
- H. Yano, A. Mizoguchi, K. Fukuda, M. Haramaki, S. Ogasawara, S. Momosaki, and M. Kojiro. The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by inducing apoptosis and arrest at the G0/G1 phase. Cancer Res. 54:448–454 (1994).
- L. Qian, T. Murakami, Y. Kimura, M. Takahashi, and K. Okita. Saikosaponin A-induced cell death of a human hepatoma cell line (HuH-7): the significance of the ‘sub-G1 peak’ in a DNA histogram. Pathol. Int. 45:207–214 (1995). CrossRef
- M. B. Sporn, and A. B. Roberts. Peptide growth factors and inflammation, tissue repair, and cancer. J. Clin. Investig. 78:329–332 (1986). CrossRef
- H. Ohshima, and H. Bartsch. Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat. Res. 305:253–264 (1994).
- G. Steinbach, P. M. Lynch, R. K. Phillips, M. H. Wallace, E. Hawk, G. B. Gordon, N. Wakabayashi, B. Saunders, Y. Shen, T. Fujimura, L. K. Su, and B. Levin. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N. Engl. J. Med. 342:1946–1952 (2000). CrossRef
- K. Muller-Decker, G. Neufang, I. Berger, M. Neumann, F. Marks, and G. Furstenberger. Transgenic cyclooxygenase-2 overexpression sensitizes mouse skin for carcinogenesis. Proc. Natl. Acad. Sci. 99:12483–12488 (2002). CrossRef
- M. E. Alvarez, A. E. Rotelli, L. E. Pelzer, J. R. Saad, and O. Giordano. Phytochemical study and anti-inflammatory properties of Lampaya hieronymi Schum. ex Moldenke II Farmaco. 55(6–7):502–505 (2000). CrossRef
- H. Xiangjiu, and R. H. Liu. Triterpenoids isolated from apple peels have potent antiproliferative activity and may be partially responsible for apple’s anticancer activity. J. Agric. Food Chem. 55(11):4366–4370 (2007). CrossRef
- T. L. Karen, M. Y. Mark, and M. B. Sporn. Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer. Nat. Rev. Cancer. 7:357–369 (2007). CrossRef
- S. D. Solomon, J. J. V. McMurray, M. A. Pfeffer, J. Wittes, R. Fowler, P. Finn, W. F. Anderson, A. Zauber, E. Hawk, and M. Bertagnolli. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N. Engl. J. Med. 352:1071–1080 (2005). CrossRef
- A. Rostom, C. Dubé, G. Lewin, A. Tsertsvadze, N. Barrowman, and C. Code. Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic review prepared for the U.S. preventive services task force. Ann. Intern. Medicine. 146:376–89 (2007).
- Chemoprevention of Colon Carcinogenesis by Oleanolic Acid and Its Analog in Male F344 Rats and Modulation of COX-2 and Apoptosis in Human Colon HT-29 Cancer Cells
Volume 25, Issue 9 , pp 2151-2157
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- colon cancer
- Industry Sectors
- Author Affiliations
- 1. Department of Medicine, Hem–Onc Section, OU Cancer Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, 73104, USA
- 2. Chemopreventive Agent Development Research Group, Division of Cancer Prevention, NCI, NIH, Bethesda, Maryland, USA
- 3. OU Cancer Institute, OUHSC, 975 NE 10th Street, BRC Building, Room 1203, Oklahoma City, Oklahoma, 73104, USA