DOI QR코드

DOI QR Code

Loquat (Eriobotrya japonica) leaf extract inhibits the growth of MDA-MB-231 tumors in nude mouse xenografts and invasion of MDA-MB-231 cells

  • You, Mi-Kyoung (Department of Food and Nutrition / Research Institute of Human Ecology, Mokpo National University) ;
  • Kim, Min-Sook (Hisol) ;
  • Jeong, Kyu-Shik (Department of Pathology, College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Eun (Korea INSpharm Research institute) ;
  • Kim, Yong-Jae (Korea INSpharm Research institute) ;
  • Kim, Hyeon-A (Department of Food and Nutrition / Research Institute of Human Ecology, Mokpo National University)
  • Received : 2015.06.16
  • Accepted : 2015.10.28
  • Published : 2016.04.01

Abstract

BACKGROUND/OBJECFTIVES: The present study was conducted to examine the inhibitory effect of loquat leaves on MDA-MB-231 cell proliferation and invasion. MATERIALS/METHODS: Female athymic nude mice were given a subcutaneous (s.c.) inoculation of MDA-MB-231 cells and randomly grouped to receive a s.c. injection of either 500 mg/kg ethanol, water extract or vehicle five times a week. Tumor growth, mitotic rate and necrosis were examined. MDA-MB-231 cells were cultured with DMSO or with various concentrations of loquat water or ethanol extract. Proliferation, adhesion, migration, invasion and matrix metalloproteinase (MMP) activity were examined. RESULTS: Tumor growth of xenograft nude mouse was significantly reduced by loquat extracts. The results of mitotic examination revealed that loquat extracts reduced tumor cell division. Both ethanol and water extracts significantly inhibited MDA-MB-231 cell proliferation. The protein expression of ErbB3 was significantly down-regulated by loquat leaf extracts. Loquat leaf extracts increased apoptosis of MDA-MB-231 cells following 24 hour incubation and the ethanol extract was more potent in inducing apoptosis than the water extract. Furthermore, loquat extracts inhibited adhesion, migration and invasion of MDA-MB-231 cells. MMP activity was significantly inhibited by loquat extracts. CONCLUSION: Our results show that extracts of loquat inhibit the growth of tumor in MDA-MB-231 xenograft nude mice and the invasion of human breast cancer cells, indicating the inhibition of tumor cell proliferation and invasion.

Acknowledgement

Supported by : ministry of Education, Science Technology (MEST), Korea Institute for Advancement of Technology (KIAT)

References

  1. Radisky ES, Radisky DC. Matrix metalloproteinase-induced epithelialmesenchymal transition in breast cancer. J Mammary Gland Biol Neoplasia 2010;15:201-12. https://doi.org/10.1007/s10911-010-9177-x
  2. Tomaskovic-Crook E, Thompson EW, Thiery JP. Epithelial to mesenchymal transition and breast cancer. Breast Cancer Res 2009;11:213. https://doi.org/10.1186/bcr2416
  3. Fidler IJ. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer 2003;3:453-8. https://doi.org/10.1038/nrc1098
  4. Geho DH, Bandle RW, Clair T, Liotta LA. Physiological mechanisms of tumor-cell invasion and migration. Physiology (Bethesda) 2005;20:194-200. https://doi.org/10.1152/physiol.00009.2005
  5. Weber GF. Molecular mechanisms of metastasis. Cancer Lett 2008;270:181-90. https://doi.org/10.1016/j.canlet.2008.04.030
  6. Kim MS, You MK, Rhuy DY, Jeong KS, Kim YJ, Baek HY, Kim HA. Oral administration of loquat suppresses DMBA-induced breast cancer in rats. Food Sci Biotechnol 2011;20:491-7. https://doi.org/10.1007/s10068-011-0068-8
  7. Liang ZZ, Aquino R, Feo VD, Simone FD, Pizza C. Polyhydroxylated Triterpenes from Eriobotrya japonica. Planta Med 1990;56:330-2. https://doi.org/10.1055/s-2006-960973
  8. Shimizu M, Uemitsu N, Shirota M, Matsumoto K, Tezuka Y. A new triterpene ester from Eriobotrya japonica. Chem Pharm Bull (Tokyo) 1996;44:2181-2. https://doi.org/10.1248/cpb.44.2181
  9. Banno N, Akihisa T, Tokuda H, Yasukawa K, Taguchi Y, Akazawa H, Ukiya M, Kimura Y, Suzuki T, Nishino H. Anti-inflammatory and antitumor-promoting effects of the triterpene acids from the leaves of Eriobotrya japonica. Biol Pharm Bull 2005;28:1995-9. https://doi.org/10.1248/bpb.28.1995
  10. Ito H, Kobayashi E, Takamatsu Y, Li SH, Hatano T, Sakagami H, Kusama K, Satoh K, Sugita D, Shimura S, Itoh Y, Yoshida T. Polyphenols from Eriobotrya japonica and their cytotoxicity against human oral tumor cell lines. Chem Pharm Bull (Tokyo) 2000;48:687-93. https://doi.org/10.1248/cpb.48.687
  11. Kim MS, You MK, Rhuy DY, Kim YJ, Baek HY, Kim HA. Loquat (Eriobotrya japonica) extracts suppress the adhesion, migration and invasion of human breast cancer cell line. Nutr Res Pract 2009;3:259-64. https://doi.org/10.4162/nrp.2009.3.4.259
  12. Park JK, Ki MR, Lee EM, Kim AY, You SY, Han SY, Lee EJ, Hong IH, Kwon SH, Kim SJ, Rando TA, Jeong KS. Losartan improves adipose tissue-derived stem cell niche by inhibiting transforming growth factor-${\beta}$ and fibrosis in skeletal muscle injury. Cell Transplant 2012;21:2407-24. https://doi.org/10.3727/096368912X637055
  13. Leek RD, Landers RJ, Harris AL, Lewis CE. Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast. Br J Cancer 1999:79;991-5. https://doi.org/10.1038/sj.bjc.6690158
  14. Zhang ZR, Al Zaharna M, Wong MM, Chiu SK, Cheung HY. Taxifolin enhances andrographolide-induced mitotic arrest and apoptosis in human prostate cancer cells via spindle assembly checkpoint activation. PLoS One 2013;8:e54577. https://doi.org/10.1371/journal.pone.0054577
  15. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 2005;5:341-54. https://doi.org/10.1038/nrc1609
  16. Holbro T, Beerli RR, Maurer F, Koziczak M, Barbas CF 3rd, Hynes NE. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci U S A 2003;100:8933-8. https://doi.org/10.1073/pnas.1537685100
  17. Hynes NE, MacDonald G. ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol 2009;21:177-84. https://doi.org/10.1016/j.ceb.2008.12.010
  18. Liu J. Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 1995;49:57-68. https://doi.org/10.1016/0378-8741(95)90032-2
  19. Taniguchi S, Imayoshi Y, Kobayashi E, Takamatsu Y, Ito H, Hatano T, Sakagami H, Tokuda H, Nishino H, Sugita D, Shimura S, Yoshida T. Production of bioactive triterpenes by Eriobotrya japonica calli. Phytochemistry 2002;59:315-23. https://doi.org/10.1016/S0031-9422(01)00455-1
  20. Ministry of Food and Drug Safety (KR). The Korean Pharmacopoeia. 10th ed. Seoul: Yakup Daily; 2013. p.50-1.
  21. Kim KH, Seo HS, Choi HS, Choi I, Shin YC, Ko SG. Induction of apoptotic cell death by ursolic acid through mitochondrial death pathway and extrinsic death receptor pathway in MDA-MB-231 cells. Arch Pharm Res 2011;34:1363-72. https://doi.org/10.1007/s12272-011-0817-5
  22. Shanmugam MK, Dai X, Kumar AP, Tan BK, Sethi G, Bishayee A. Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies. Biochem Pharmacol 2013;85:1579-87. https://doi.org/10.1016/j.bcp.2013.03.006
  23. Shan JZ, Xuan YY, Ruan SQ, Sun M. Proliferation-inhibiting and apoptosis-inducing effects of ursolic acid and oleanolic acid on multi-drug resistance cancer cells in vitro. Chin J Integr Med 2011;17:607-11. https://doi.org/10.1007/s11655-011-0815-y
  24. Meng Q, Goldberg ID, Rosen EM, Fan S. Inhibitory effects of Indole-3-carbinol on invasion and migration in human breast cancer cells. Breast Cancer Res Treat 2000;63:147-52. https://doi.org/10.1023/A:1006495824158
  25. Johansson N, Ahonen M, Kahari VM. Matrix metalloproteinases in tumor invasion. Cell Mol Life Sci 2000;57:5-15. https://doi.org/10.1007/s000180050495
  26. Yeh CT, Wu CH, Yen GC. Ursolic acid, a naturally occurring triterpenoid, suppresses migration and invasion of human breast cancer cells by modulating c-Jun N-terminal kinase, Akt and mammalian target of rapamycin signaling. Mol Nutr Food Res 2010;54:1285-95. https://doi.org/10.1002/mnfr.200900414
  27. Cos S, Fernandez R, Guezmes A, Sanchez-Barcelo EJ. Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells. Cancer Res 1998;58:4383-90.

Cited by

  1. Induction of apoptosis by ethanol extract of Evodia rutaecarpa in HeLa human cervical cancer cells via activation of AMP-activated protein kinase vol.10, pp.6, 2016, https://doi.org/10.5582/bst.2016.01170
  2. Ethanol extract of loquat fruit skin inhibits the proliferation and metastatic potential of EJ human bladder carcinoma cells vol.21, pp.5, 2017, https://doi.org/10.1080/19768354.2017.1358665
  3. Reversal of Multidrug Resistance in Human Colon Cancer and Human Leukemia Cells by Three Plant Extracts and Their Major Secondary Metabolites vol.5, pp.4, 2018, https://doi.org/10.3390/medicines5040123