Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Morin, a Flavonoid from Moraceae, Inhibits Cancer Cell Adhesion to Endothelial Cells and EMT by Down-regulating VCAM-1 and N-cadherin

  • Lee, Jeong-Hee (Department of Pathology, Institute of Health Sciences) ;
  • Jin, Hana (Department of Pharmacology, Institute of Health Sciences) ;
  • Lee, Won Sup (Department of Internal Medicine, Institute of Health Sciences) ;
  • Nagappan, Arulkumar (Department of Internal Medicine, Institute of Health Sciences) ;
  • Choi, Yung Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine and Department of Biomaterial Control (BK21 program), Dongeui University Graduate School) ;
  • Kim, GonSup (School of Veterinary Medicine, Gyeongsang National University School of Medicine) ;
  • Jung, Jin-Myung (Department of Neurosurgery, Institute of Health Sciences) ;
  • Ryu, Chung Ho (Division of Applied Life Science (BK 21 Program), Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • Shin, Sung Chul (Department of Chemistry, and Research Institute of Life Science, Gyeongsang National University School of Medicine) ;
  • Hong, SoonChan (Department of Surgery, Institute of Health Sciences) ;
  • Kim, Hye Jung (Department of Pharmacology, Institute of Health Sciences)
  • Published : 2016.07.01
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Abstract

Morin, a flavonoid found in figs and other Moraceae species, displays a variety of biological actions, exerting anti-oxidant, anti-inflammatory and anti-carcinogenic effects. Here, we investigated the anti-cancer activity of morin focusing on anti-adhesive influence. We performed experiments with MDA-MB-231 human breast cancer cells. Morin inhibited TNF-induced cancer cell adhesion to human umbilical vein endothelial cells (HUVECs) without showing any toxicity. It further inhibited the expression of VCAM-1 on MDA-MB-231 cells as well as HUVECs. Morin also decreased the expression of N-cadherin on MDA-MB-231 cells. In addition, there was apparent anti-metastatic activity in vivo. In conclusion, this study suggested that morin inhibits cancer cell adhesion to HUVECs by reducing VCAM-1, and EMT by targeting N-cadherin, and that it features anti-metastatic activity in vivo. Further investigation of possible anti-metastatic activity of morin against human breast cancer cells is warranted.

Keywords

Acknowledgement

Supported by : Ministry of Health & Welfar

References

  1. Ahmad M, Zhang Y, Papharalambus C, et al (2002). Role of isoprenylcysteine carboxyl methyltransferase in tumor necrosis factor-alpha stimulation of expression of vascular cell adhesion molecule-1 in endothelial cells. Arterioscler Thromb Vasc Biol, 22, 759-64. https://doi.org/10.1161/01.ATV.0000015884.61894.DC
  2. Anandappa SY, Sibson R, Platt-Higgins A, et al (2000). Variant estrogen receptor alpha mRNAs in human breast cancer specimens. Int J Cancer, 88, 209-16. https://doi.org/10.1002/1097-0215(20001015)88:2<209::AID-IJC10>3.0.CO;2-M
  3. Chang LW, Juang LJ, Wang BS, et al (2011). Antioxidant and antityrosinase activity of mulberry (Morus alba L.) twigs and root bark. Food and chemical toxicology : an international journal published for the British. Industrial Biological Res Associat, 49, 785-90.
  4. Correia M, Cravo M, Marques-Vidal P, et al (2007). Serum concentrations of TNF-alpha as a surrogate marker for malnutrition and worse quality of life in patients with gastric cancer. Clin Nutr, 26, 728-35. https://doi.org/10.1016/j.clnu.2007.08.014
  5. Jin H, Lee WS, Eun SY, et al (2014). Morin, a flavonoid from Moraceae, suppresses growth and invasion of the highly metastatic breast cancer cell line MDA-MB231 partly through suppression of the Akt pathway. Int J Oncol.
  6. Klemke M, Weschenfelder T, Konstandin MH, et al (2007). High affinity interaction of integrin alpha4beta1 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) enhances migration of human melanoma cells across activated endothelial cell layers. J Cell Physiol, 212, 368-74. https://doi.org/10.1002/jcp.21029
  7. Kundu JK, Chun KS (2014). The Promise of Dried Fruits in Cancer Chemoprevention. Asian Pac J Cancer Prev, 15, 3343-52. https://doi.org/10.7314/APJCP.2014.15.8.3343
  8. Liu BL, Zhang X, Zhang W, et al (2007). New enlightenment of French Paradox: resveratrol's potential for cancer chemoprevention and anti-cancer therapy. Cancer Biol Ther, 6, 1833-6. https://doi.org/10.4161/cbt.6.12.5161
  9. Lu JN, Lee WS, Kim MJ, et al (2014). The inhibitory effect of anthocyanins on Akt on invasion and epithelial-mesenchymal transition is not associated with the anti-EGFR effect of the anthocyanins. Int J Oncol, 44, 1756-66. https://doi.org/10.3892/ijo.2014.2315
  10. Manna SK, Aggarwal RS, Sethi G, et al (2007). Morin (3,5,7,2',4'-Pentahydroxyflavone) abolishes nuclear factorkappaB activation induced by various carcinogens and inflammatory stimuli, leading to suppression of nuclear factor-kappaB-regulated gene expression and up-regulation of apoptosis. Clin Cancer Res, 13, 2290-7. https://doi.org/10.1158/1078-0432.CCR-06-2394
  11. Nicolson GL (1988). Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites. Cancer Metastasis Rev, 7, 143-88. https://doi.org/10.1007/BF00046483
  12. Okegawa T, Pong RC, Li Y, et al (2004). The role of cell adhesion molecule in cancer progression and its application in cancer therapy. Acta Biochim Pol, 51, 445-57.
  13. Orr FW, Wang HH, Lafrenie RM, et al (2000). Interactions between cancer cells and the endothelium in metastasis. J Pathol, 190, 310-29. https://doi.org/10.1002/(SICI)1096-9896(200002)190:3<310::AID-PATH525>3.0.CO;2-P
  14. Prasad S, Tyagi AK, Aggarwal BB (2014). Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer Res Treat, 46, 2-18. https://doi.org/10.4143/crt.2014.46.1.2
  15. Sivaramakrishnan V, Niranjali Devaraj S (2009). Morin regulates the expression of NF-kappaB-p65, COX-2 and matrix metalloproteinases in diethylnitrosamine induced rat hepatocellular carcinoma. Chemico-Biological Interactions, 180, 353-9. https://doi.org/10.1016/j.cbi.2009.02.004
  16. Stavric B (1994). Role of chemopreventers in human diet. Clinical Biochemistry, 27, 319-32. https://doi.org/10.1016/0009-9120(94)00039-5
  17. Su CY, Li YS, Han Y, et al (2014). Correlation between expression of cell adhesion molecules CD(4)(4) v6 and E-cadherin and lymphatic metastasis in non- small cell lung cancer. Asian Pac J Cancer Prev, 15, 2221-4. https://doi.org/10.7314/APJCP.2014.15.5.2221
  18. Youn GS, Kwon DJ, Ju SM, et al (2013). Curcumin ameliorates TNF-alpha-induced ICAM-1 expression and subsequent THP-1 adhesiveness via the induction of heme oxygenase-1 in the HaCaT cells. BMB reports, 46, 410-5. https://doi.org/10.5483/BMBRep.2013.46.8.014
  19. Zhang YY, Chen B, Ding YQ (2012). Metastasis-associated factors facilitating the progression of colorectal cancer. Asian Pac J Cancer Prev, 13, 2437-44. https://doi.org/10.7314/APJCP.2012.13.6.2437