Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Lycopene Inhibits Proliferation, Invasion and Migration of Human Breast Cancer Cells

  • Koh, Min-Soo (College of Pharmacy, Duksung Women's University) ;
  • Hwang, Jin-Sun (College of Pharmacy, Duksung Women's University) ;
  • Moon, A-Ree (College of Pharmacy, Duksung Women's University)
  • Published : 2010.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

Breast cancer has been estimated as one of the most common causes of cancer death among women. The major cause of death from breast cancer is the metastatic spread of the disease from the primary tumor to distant sites in the body. Lycopene is one of the major carotenoids in fruits and vegetables including tomatoes. Epidemiological studies have shown that the dietary intake of lycopene is associated with decreased risk of cancer. Although mounting evidence shows the chemopreventive effect of lycopene, the role of lycopene in the prevention of metastatic potential of breast cancer has not been determined yet. In the present study, we investigated the inhibitory effect of lycopene on invasive and migratory phenotypes of two highly aggressive breast cancer cell lines, H-Ras-transformed MCF10A human breast epithelial cells (H-Ras MCF10A) and MDA-MB-231 human breast cancer cells. Here, we report that lycopene significantly inhibits invasion and migration as well as proliferation of H-Ras MCF10A and MDA-MB-231 cells. This study suggested an in vitro anti-cancer and anti-metastatic potential of lycopene. We also showed that activations of ERKs and Akt were inhibited by lycopene in H-Ras MCF10A cells, suggesting that the ERKs and Akt signaling pathways may be involved in lycopene-induced anti-proliferative and/or anti-invasive/migratory effects in these cells. Taken in conjunction with the fact that breast cancer metastasis is one of the most lethal malignancies in women, our findings may provide useful information for the application of lycopene in establishing strategy to prevent the metastatic breast cancer.

Keywords

References

  1. Agarwal, S. and Rao, V. A. (2000). Tomato lycopene and its role in human health and chronic diseases. CMJA. 163, 739-744.
  2. Arab, L. and Steck, S. (2000). Lycopene and cardiovascular disease. Am. J. Clin. Nutr. 71 Suppl, 1691S-1695S. https://doi.org/10.1093/ajcn/71.6.1691S
  3. Boileau, A. C., Merchen, N. R., Wasson, K., Atkinson, C. A. and Erdman, J. W. (1999). Cis-lycopene is more bioavailable than trans-lycopene in vitro and in vivo in lymph-cannulated ferrets. J. Nutr. 129, 1176-1181. https://doi.org/10.1093/jn/129.6.1176
  4. Chan, C. M., Fang, J. Y., Lin, H. H., Yang, C. Y. and Hung, C. F. (2009). Lycopene inhibits PDGF-BB-induced retinal pigment epithelial cell migration by suppression of PI3K/Akt and MAPK pathways. Biochem. Biophys. Res. Commun. 388, 172-176. https://doi.org/10.1016/j.bbrc.2009.07.155
  5. Chiang, H. S., Wu, W. B., Fang, J. Y., Chen, D. F., Chen, B. H., Huang, C. C., Chen, Y. T. and Hung, C. F. (2007). Lycopene inhibits PDGF-BB-induced signaling and migration in human dermal fibroblasts through interaction with PDGF-BB. Life Sci. 81, 1509-1517. https://doi.org/10.1016/j.lfs.2007.09.018
  6. Clair, T., Miller, W. and Cho-Chung, Y. (1987). Prognostic significance of the expression of the ras protein with a molecular weight of 21,000 by human breast cancer. Cancer Res. 49, 5290-5293.
  7. Cunningham, F. X. Jr., Sun, Z., Chamovitz, D., Hirschberg, J. and Gantt, E. (1994). Molecular structure and enzymatic function of lycopene cyclase from the Cyanobacterium Synechococcus sp Strain PCC7942. Plant. Cell. 6, 1107-1121. https://doi.org/10.1105/tpc.6.8.1107
  8. DeClerck, Y. A., Perez, N., Shimada, H., Boone, T. C., Langley, K. E. and Taylor, S. M. (1992). Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases. Cancer Res. 52, 701-708.
  9. Ferguson, L. R. (1994). Antimutagens as cancer chemopreventive agents in the diet. Mut. Res. 307, 395-410. https://doi.org/10.1016/0027-5107(94)90313-1
  10. Franceschi, S., Bidoli, E., LaVeccia, C., Talamini, R., D'Avanzo, B. and Negri, E. (1994). Tomatoes and risk of digestive tract cancers. Int. J. Cancer 59, 181-184. https://doi.org/10.1002/ijc.2910590207
  11. Freemantle, S. J., Spinella, M. J. and Dmitrovsky, E. (2003). Retinoids in cancer therapy and chemoprevention: promise meets resistance. Oncogene 22, 7305-7315. https://doi.org/10.1038/sj.onc.1206936
  12. Giovannucci, E. (1999). Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J. Natl. Cancer Inst. 91, 317-331. https://doi.org/10.1093/jnci/91.4.317
  13. Huang, C. S., Fan, Y. E., Lin, C. Y. and Hu, M. L. (2007). Lycopene inhibits matrix metalloproteinase-9 expression and down-regulates the binding activity of nuclear factor-kappa B and stimulatory protein-1. J. Nutr. Biochem. 18, 449-456. https://doi.org/10.1016/j.jnutbio.2006.08.007
  14. Huang, C. S., Liao, J. W. and Hu, M. L. (2008). Lycopene inhibits experimental metastasis of human hepatoma SKHep-1 cells in athymic nude mice. J. Nutr. 138, 538-543. https://doi.org/10.1093/jn/138.3.538
  15. Hwang, E. S. and Bowen, P. E. (2004). Cell cycle arrest and induction of apoptosis by lycopene in LNCaP human prostate cancer cells. J. Med. Food 7, 284-289. https://doi.org/10.1089/jmf.2004.7.284
  16. Hwang, E. S. and Lee, H. J. (2006). Inhibitory effects of lycopene on the adhesion, invasion, and migration of SK-Hep1 human hepatoma cells. Exp. Biol. Med. 231, 322-327. https://doi.org/10.1177/153537020623100313
  17. Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J. and Thun, M. J. (2007). Cancer Statistics. CA Cancer J. Clin. 57, 43-66. https://doi.org/10.3322/canjclin.57.1.43
  18. Kim, E. S., Jeong, J. B., Kim, S., Lee, K. M., Ko, E., Noh, D. Y., Hwang, K. T., Ha, J. H., Lee, C. H., Kim, S. G. and Moon, A. (2010). The G12 family proteins upregulate matrix metalloproteinase-2 via p53 leading to human breast cell invasion. Breast Cancer Res. Treat. [Epub ahead of print].
  19. Kim, I. Y. and Moon, A. (2004). Inhibition of invasive phenotype and induction of apoptosis in human breast cancer cells by chemopreventive agents. J. Korean Assoc. Cancer Prev. 9, 59-67.
  20. Kim, L., Rao, A. V. and Rao, L. G. (2002). Effect of lycopene on prostate LNCaP cancer cells in culture. J. Med. Food 5, 181-187. https://doi.org/10.1089/109662002763003320
  21. Kim, M. S., Lee, E. J., Kim, H. R. and Moon, A. (2003). p38 kinase is a key signaling molecule for H-Ras-induced cell motility and invasive phenotype in human breast epithelial cells. Cancer Res. 63, 5454-5461.
  22. Levy, J., Bosin, E., Feldman, B., Giat, Y., Miinster, A., Danilenko, M. and Sharoni, Y. (1995). Lycopene is a more potent inhibitor of human cancer cell proliferation than either $\alpha$-carotene or $\beta$-carotene. Nutr. Cancer 24, 257-266. https://doi.org/10.1080/01635589509514415
  23. Liotta, L. A., Abe, S., Robey, P. G. and Martin, G. R. (1979). Preferential digestion of basement membrane collagen by an enzyme derived from a metastatic murine tumor. Proc. Natl. Acad. Sci. U.S.A. 76, 2268-2272. https://doi.org/10.1073/pnas.76.5.2268
  24. Moon, A., Kim, M. S., Kim, T. G., Kim, S. H., Kim, H. E., Chen, Y. Q. and Kim, H. R. (2000). H-ras, but not N-ras, induces an invasive phenotype in human breast epithelial cells: a role for MMP-2 in the H-ras-induced invasive phenotype. Int. J. Cancer 85, 176-181. https://doi.org/10.1002/(SICI)1097-0215(20000115)85:2%3C176::AID-IJC5%3E3.0.CO;2-E
  25. Nagasawa, H., Mitamura, T., Sakamoto, S. and Yamamoto, K. (1995). Effects of lycopene on spontaneous mammary tumor development in SHN virgin mice. Anticancer Res. 15, 1173-1178.
  26. Omoni, O. A. and Aluko, E. R. (2005). The anti-carcinogenic and anti-atherogenic effects of lycopene: a review. Trends Food Sci. Technol. 16, 344-350. https://doi.org/10.1016/j.tifs.2005.02.002
  27. Prakash, P., Russell, R. M. and Krinsky, N. I. (2001). In vitro inhibition of proliferation of estrogen-dependent and estrogen-independent human breast cancer cells treated with carotenoids or retinoids. J. Nutr. 131, 1574-1580. https://doi.org/10.1093/jn/131.5.1574
  28. Rao, A. V. and Agarwal, S. (1999). Role of lycopene as antioxidant carotenoid in the prevention of chronic diseases: a review. Nut. Res. 19, 305-323. https://doi.org/10.1016/S0271-5317(98)00193-6
  29. Rao, A. V. and Agarwal, S. (2000). Role of anti-oxidant lycopene in cancer and heart disease. J. Am. Coll. Nutr. 19, 563-569. https://doi.org/10.1080/07315724.2000.10718953
  30. Salman, H., Bergman, M., Djaldetti, M. and Bessler, H. (2007). Lycopene affects proliferation and apoptosis of four malignant cell lines. Biomed. Pharmacother. 61, 366-369. https://doi.org/10.1016/j.biopha.2007.02.015
  31. Shi, J. (2000). Lycopene in tomatoes: chemical and physical properties affected by food processing. Crit. Rev. Food Sci. Nutr. 40, 1-42. https://doi.org/10.1080/10408690091189275
  32. Shin, I., Kim, S., Song, H., Kim, H. R. and Moon, A. (2005). H-Ras-specific activation of Rac-MKK3/6-p38 pathway: its critical role in invasion and migration of breast epithelial cells. J. Biol. Chem. 280, 14675-14683. https://doi.org/10.1074/jbc.M411625200
  33. Song, H., Ki, S. H., Kim, S. G. and Moon, A. (2006). Activating transcription factor 2 mediates matrix metalloproteinase-2 transcriptional activation induced by p38 in breast epithelial cells. Cancer Res. 66, 10487-10496. https://doi.org/10.1158/0008-5472.CAN-06-1461
  34. Stahl, W. and Sies, H. (1996). Lycopene: a biologically important carotenoid for humans? Arch. Biochem. Biophys. 336, 1-9. https://doi.org/10.1006/abbi.1996.0525
  35. Stavric, B. (1994). Role of chemopreventers in human diet. Clinical Biochem. 27, 319-332. https://doi.org/10.1016/0009-9120(94)00039-5
  36. Stetler-Stevenson, W. G., Aznavoorian, S. and Liotta, L. A. (1993). Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu. Rev. Cell Biol. 9, 541-557. https://doi.org/10.1146/annurev.cb.09.110193.002545
  37. Weisburger, J. H. (2002). Lycopene and tomato products in health promotion. Exp. Biol. Med. 227, 924-927. https://doi.org/10.1177/153537020222701014
  38. Wu, K., Schwatz, S. J., Platz, E. A., Clinton, S. K., Erdman, J. W., Ferruzzi, M. G., Willett W. C. and Giovannucci E. L. (2003). Variations in plasma lycopene and specific isomers over time in a cohort of US men. J. Nutr. 133, 1930-1936. https://doi.org/10.1093/jn/133.6.1930
  39. Yang, E. and Korsmeyer, S. J. (1996). Molecular thanatopsis: a discourse on the BCL2 family and cell death. Blood. 88, 386-401.

Cited by

  1. Anti-inflammatory effect of lycopene in SW480 human colorectal cancer cells vol.11, pp.2, 2017, https://doi.org/10.4162/nrp.2017.11.2.90
  2. Transglutaminase-2 induces N-cadherin expression in TGF-β1-induced epithelial mesenchymal transition via c-Jun-N-terminal kinase activation by protein phosphatase 2A down-regulation vol.49, pp.7, 2013, https://doi.org/10.1016/j.ejca.2012.11.036
  3. Physiological Activities of Saccharified Cherry Tomato Gruel Containing Different Levels of Cherry Tomato Puree vol.28, pp.6, 2012, https://doi.org/10.9724/kfcs.2012.28.6.773
  4. Involvement of Src and the actin cytoskeleton in the antitumorigenic action of adenosine dialdehyde vol.85, pp.8, 2013, https://doi.org/10.1016/j.bcp.2013.01.012
  5. Natural Products for Chemoprevention of Breast Cancer vol.20, pp.4, 2015, https://doi.org/10.15430/JCP.2015.20.4.223
  6. Fruit and vegetable intake and breast cancer prognosis: a meta-analysis of prospective cohort studies vol.117, pp.05, 2017, https://doi.org/10.1017/S0007114517000423
  7. Tomato and Tomato Byproducts. Human Health Benefits of Lycopene and Its Application to Meat Products: A Review vol.54, pp.8, 2014, https://doi.org/10.1080/10408398.2011.623799
  8. Phenolic Profile of Edible Honeysuckle Berries (Genus Lonicera) and Their Biological Effects vol.17, pp.1, 2011, https://doi.org/10.3390/molecules17010061
  9. Bioactivities of phytochemicals present in tomato vol.55, pp.8, 2018, https://doi.org/10.1007/s13197-018-3221-z
  10. New Insights into Molecular Mechanism behind Anti-Cancer Activities of Lycopene vol.26, pp.13, 2010, https://doi.org/10.3390/molecules26133888