Loquat (Eriobotrya japonica) leaf extract inhibits the growth of MDA-MB-231 tumors in nude mouse xenografts and invasion of MDA-MB-231 cells
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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.
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.
참고문헌 (27)
- Radisky ES, "Matrix metalloproteinase-induced epithelialmesenchymal transition in breast cancer", J Mammary Gland Biol Neoplasia, 15, pp.201~212 (2010)
- Tomaskovic-Crook E, "Epithelial to mesenchymal transition and breast cancer", Breast Cancer Res, 11, pp.213~ (2009)
- Fidler IJ., "The pathogenesis of cancer metastasis: the ‘seed and soil’hypothesis revisited", Nat Rev Cancer, 3, pp.453~458 (2003)
- Geho DH, "Physiological mechanisms of tumor-cell invasion and migration", Physiology (Bethesda), 20, pp.194~200 (2005)
- Weber GF., "Molecular mechanisms of metastasis", Cancer Lett, 270, pp.181~190 (2008)
- 김민숙, "Oral Administration of Loquat Suppresses DMBA-induced Breast Cancer in Rats", Food Science and Biotechnology, 20(2), pp.491~497 (2011), 한국식품과학회
- Liang ZZ, "Polyhydroxylated Triterpenes from Eriobotrya japonica", Planta Med, 56, pp.330~332 (1990)
- Shimizu M, "A new triterpene ester from Eriobotrya japonica", Chem Pharm Bull (Tokyo), 44, pp.2181~2182 (1996)
- Banno N, "Anti-inflammatory and antitumor-promoting effects of the triterpene acids from the leaves of Eriobotrya japonica", Biol Pharm Bull, 28, pp.1995~1999 (2005)
- Ito H, "Polyphenols from Eriobotrya japonica and their cytotoxicity against human oral tumor cell lines", Chem Pharm Bull (Tokyo), 48, pp.687~693 (2000)
- 김민숙, "Loquat (Eriobotrya japonica) extracts suppress the adhesion, migration and invasion of human breast cancer cell line", Nutrition Research and Practice, 3(4), pp.259~264 (2009), 한국영양학회
- Park JK, "Losartan improves adipose tissue-derived stem cell niche by inhibiting transforming growth factor-β and fibrosis in skeletal muscle injury", Cell Transplant, 21, pp.2407~2424 (2012)
- Leek RD, "Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast", Br J Cancer, 79, pp.991~995 (1999)
- Zhang ZR, "Taxifolin enhances andrographolide-induced mitotic arrest and apoptosis in human prostate cancer cells via spindle assembly checkpoint activation", PLoS One, 8, pp.e54577~ (2013)
- Hynes NE, "ERBB receptors and cancer: the complexity of targeted inhibitors", Nat Rev Cancer, 5, pp.341~354 (2005)
- Holbro T, "The ErbB2", ErbB3 heterodimer functions as an oncogenic unit:ErbB2 requires ErbB3 to drive breast tumor cell proliferation, 2003, pp.100, 8933~8938
- Hynes NE, "ErbB receptors and signaling pathways in cancer", Curr Opin Cell Biol, 21, pp.177~184 (2009)
- Liu J., "Pharmacology of oleanolic acid and ursolic acid", J Ethnopharmacol, 49, pp.57~68 (1995)
- Taniguchi S, "Production of bioactive triterpenes by Eriobotrya japonica calli", Phytochemistry, 59, pp.315~323 (2002)
- Ministry of Food and Drug Safety (KR), "The Korean Pharmacopoeia", pp.50~51 (2013), Yakup Daily
- Kyung Hun Kim, "Induction of Apoptotic Cell Death by Ursolic Acid through Mitochondrial Death Pathway and Extrinsic Death Receptor Pathway in MDA-MB-231 Cells", Archives of Pharmacal Research, 34(8), pp.1363~1372 (2011), 대한약학회
- Shanmugam MK, "Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies", Biochem Pharmacol, 85, pp.1579~1587 (2013)
- Shan JZ, "Proliferation-inhibiting and apoptosis-inducing effects of ursolic acid and oleanolic acid on multi-drug resistance cancer cells in vitro", Chin J Integr Med, 17, pp.607~611 (2011)
- Meng Q, "Inhibitory effects of Indole-3-carbinol on invasion and migration in human breast cancer cells", Breast Cancer Res Treat, 63, pp.147~152 (2000)
- Johansson N, "Matrix metalloproteinases in tumor invasion", Cell Mol Life Sci, 57, pp.5~15 (2000)
- Yeh CT, "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, 54, pp.1285~1295 (2010)
- Cos S, "Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells", Cancer Res, 58, pp.4383~4390 (1998)