DOI QR코드

DOI QR Code

Antiproliferative properties of luteolin against chemically induced colon cancer in mice fed on a high-fat diet and colorectal cancer cells grown in adipocyte-derived medium

  • Park, Jeongeun (Department of Food Science and Nutrition, Daegu Catholic University) ;
  • Kim, Eunjung (Department of Food Science and Nutrition, Daegu Catholic University)
  • 투고 : 2021.12.11
  • 심사 : 2022.01.07
  • 발행 : 2022.02.28

초록

Purpose: Obesity and a high-fat diet (HFD) are risk factors for colorectal cancer. We have previously shown that luteolin (LUT) supplementation in HFD-fed mice markedly inhibits tumor development in chemically induced colon carcinogenesis. In this study, we evaluated the anticancer effect of LUT in the inhibition of cell proliferation in HFD-fed obese mice and HT-29 human colorectal adenocarcinoma cells grown in an adipocyte-derived medium. Methods: C57BL/6 mice were fed a normal diet (ND, 11.69% fat out of total calories consumed, n = 10), HFD (40% fat out of total calories consumed, n = 10), HFD with 0.0025% LUT (n = 10), and HFD with 0.005% LUT (n = 10) and were subjected to azoxymethane-dextran sulfate sodium chemical colon carcinogenesis. All mice were fed the experimental diet for 11 weeks. 3T3-L1 preadipocytes and HT-29 cells were treated with various doses of LUT in an adipocyte-conditioned medium (Ad-CM). Results: The weekly body weight changes in the LUT groups were similar to those in the HFD group; however, the survival rates of the LUT group were higher than those of the HFD group. Impaired crypt integrity of the colonic mucosa in the HFD group was observed to be restored in the LUT group. The colonic expression of proliferating cell nuclear antigen and insulin-like growth factor 1 (IGF-1) receptors were suppressed by the LUT supplementation in the HFD-fed mice. The LUT treatment (10, 20, and 40 µM) inhibited the proliferation and migration of HT-29 cells cultured in Ad-CM in a dose-dependent manner, as well as the differentiation of 3T3-L1 preadipocytes. Conclusion: These results suggest that the anticancer effect of LUT is probably due to the inhibition of IGF-1 signaling and adipogenesis-related cell proliferation in colon cancer cells.

키워드

과제정보

This work was supported by research grants from Daegu Catholic University in 2019.

참고문헌

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424. https://doi.org/10.3322/caac.21492
  2. Boyle P, Langman JS. ABC of colorectal cancer: Epidemiology. BMJ 2000; 321(7264): 805-808. https://doi.org/10.1136/bmj.321.7264.805
  3. Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg 2009; 22(4): 191-197. https://doi.org/10.1055/s-0029-1242458
  4. Larsson SC, Wolk A. Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies. Am J Clin Nutr 2007; 86(3): 556-565. https://doi.org/10.1093/ajcn/86.3.556
  5. Sung MK, Yeon JY, Park SY, Park JH, Choi MS. Obesity-induced metabolic stresses in breast and colon cancer. Ann N Y Acad Sci 2011; 1229(1): 61-68. https://doi.org/10.1111/j.1749-6632.2011.06094.x
  6. Moghaddam AA, Woodward M, Huxley R. Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomarkers Prev 2007; 16(12): 2533-2547. https://doi.org/10.1158/1055-9965.EPI-07-0708
  7. Baltgalvis KA, Berger FG, Pena MM, Davis JM, Carson JA. The interaction of a high-fat diet and regular moderate intensity exercise on intestinal polyp development in ApcMin/+ mice. Cancer Prev Res (Phila) 2009; 2(7): 641-649. https://doi.org/10.1158/1940-6207.capr-09-0017
  8. Padidar S, Farquharson AJ, Williams LM, Kearney R, Arthur JR, Drew JE. High-fat diet alters gene expression in the liver and colon: links to increased development of aberrant crypt foci. Dig Dis Sci 2012; 57(7): 1866-1874. https://doi.org/10.1007/s10620-012-2092-9
  9. Jochem C, Leitzmann M. Obesity and colorectal cancer. Recent Results Cancer Res 2016; 208: 17-41. https://doi.org/10.1007/978-3-319-42542-9_2
  10. Lin Y, Shi R, Wang X, Shen HM. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr Cancer Drug Targets 2008; 8(7): 634-646. https://doi.org/10.2174/156800908786241050
  11. Ashokkumar P, Sudhandiran G. Luteolin inhibits cell proliferation during Azoxymethane-induced experimental colon carcinogenesis via Wnt/β-catenin pathway. Invest New Drugs 2011; 29(2): 273-284. https://doi.org/10.1007/s10637-009-9359-9
  12. Manju V, Nalini N. Protective role of luteolin in 1,2-dimethylhydrazine induced experimental colon carcinogenesis. Cell Biochem Funct 2007; 25(2): 189-194. https://doi.org/10.1002/cbf.1305
  13. Zhang X, Zhang QX, Wang X, Zhang L, Qu W, Bao B, et al. Dietary luteolin activates browning and thermogenesis in mice through an AMPK/PGC1α pathway-mediated mechanism. Int J Obes 2016; 40(12): 1841-1849. https://doi.org/10.1038/ijo.2016.108
  14. Kwon EY, Jung UJ, Park T, Yun JW, Choi MS. Luteolin attenuates hepatic steatosis and insulin resistance through the interplay between the liver and adipose tissue in mice with diet-induced obesity. Diabetes 2015; 64(5): 1658-1669. https://doi.org/10.2337/db14-0631
  15. Nepali S, Son JS, Poudel B, Lee JH, Lee YM, Kim DK. Luteolin is a bioflavonoid that attenuates adipocyte-derived inflammatory responses via suppression of nuclear factor-κB/mitogen-activated protein kinases pathway. Pharmacogn Mag 2015; 11(43): 627-635. https://doi.org/10.4103/0973-1296.160470
  16. Park JE, Kim E. Effects of luteolin on chemical induced colon carcinogenesis in high fat diet-fed obese mouse. J Nutr Health 2018; 51(1): 14-22. https://doi.org/10.4163/jnh.2018.51.1.14
  17. Tanaka T, Kohno H, Suzuki R, Yamada Y, Sugie S, Mori H. A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate. Cancer Sci 2003; 94(11): 965-973. https://doi.org/10.1111/j.1349-7006.2003.tb01386.x
  18. Johnson IT, Lund EK. Review article: nutrition, obesity and colorectal cancer. Aliment Pharmacol Ther 2007; 26(2): 161-181. https://doi.org/10.1111/j.1365-2036.2007.03371.x
  19. Tang FY, Pai MH, Chiang EP. Consumption of high-fat diet induces tumor progression and epithelial-mesenchymal transition of colorectal cancer in a mouse xenograft model. J Nutr Biochem 2012; 23(10): 1302-1313. https://doi.org/10.1016/j.jnutbio.2011.07.011
  20. Moschos SJ, Mantzoros CS. The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology 2002; 63(4): 317-332. https://doi.org/10.1159/000066230
  21. Sandhu MS, Dunger DB, Giovannucci EL. Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer. J Natl Cancer Inst 2002; 94(13): 972-980. https://doi.org/10.1093/jnci/94.13.972
  22. Kajantie E, Fall CH, Seppala M, Koistinen R, Dunkel L, Yliharsila H, et al. Serum insulin-like growth factor (IGF)-I and IGF-binding protein-1 in elderly people: relationships with cardiovascular risk factors, body composition, size at birth, and childhood growth. J Clin Endocrinol Metab 2003; 88(3): 1059-1065. https://doi.org/10.1210/jc.2002-021380
  23. Guo YS, Narayan S, Yallampalli C, Singh P. Characterization of insulinlike growth factor I receptors in human colon cancer. Gastroenterology 1992; 102(4 Pt 1): 1101-1108. https://doi.org/10.1016/0016-5085(92)90744-j
  24. Hirose Y, Hata K, Kuno T, Yoshida K, Sakata K, Yamada Y, et al. Enhancement of development of azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice. Carcinogenesis 2004; 25(5): 821-825. https://doi.org/10.1093/carcin/bgh059
  25. Lim DY, Jeong Y, Tyner AL, Park JH. Induction of cell cycle arrest and apoptosis in HT-29 human colon cancer cells by the dietary compound luteolin. Am J Physiol Gastrointest Liver Physiol 2007; 292(1): G66-G75. https://doi.org/10.1152/ajpgi.00248.2006
  26. Fang J, Zhou Q, Shi XL, Jiang BH. Luteolin inhibits insulin-like growth factor 1 receptor signaling in prostate cancer cells. Carcinogenesis 2007; 28(3): 713-723. https://doi.org/10.1093/carcin/bgl189
  27. Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 2006; 6(10): 772-783. https://doi.org/10.1038/nri1937
  28. Hardwick JC, Van Den Brink GR, Offerhaus GJ, Van Deventer SJ, Peppelenbosch MP. Leptin is a growth factor for colonic epithelial cells. Gastroenterology 2001; 121(1): 79-90. https://doi.org/10.1053/gast.2001.25490
  29. Liu Z, Uesaka T, Watanabe H, Kato N. High fat diet enhances colonic cell proliferation and carcinogenesis in rats by elevating serum leptin. Int J Oncol 2001; 19(5): 1009-1014.
  30. Rouet-Benzineb P, Aparicio T, Guilmeau S, Pouzet C, Descatoire V, Buyse M, et al. Leptin counteracts sodium butyrate-induced apoptosis in human colon cancer HT-29 cells via NF-κB signaling. J Biol Chem 2004; 279(16): 16495-16502. https://doi.org/10.1074/jbc.M312999200
  31. Park HS, Kim SH, Kim YS, Ryu SY, Hwang JT, Yang HJ, et al. Luteolin inhibits adipogenic differentiation by regulating PPARγ activation. Biofactors 2009; 35(4): 373-379. https://doi.org/10.1002/biof.38