ANTI-INVASIVE EFFECT OF Catharanthus roseus EXTRACT ON HIGHLY METASTATIC HUMAN BREAST CANCER MDA-MB-231 CELLS

Authors

  • Nagla Mustafa Eltayeb Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
  • Shy Yee Ng Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
  • Zhari Ismail Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia
  • Salizawati Muhamad Salhimi Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia

DOI:

https://doi.org/10.11113/jt.v78.9870

Keywords:

Catharanthus roseus, MTS, zymography, MMP -2, MMP-9, MDA-MB-231.

Abstract

Catharanthus roseus (C. roseus) is an important medicinal plant contains a lot of useful alkaloids. The objective of this study is to determine the effect of Catharanthus roseus leaves extract on the MDA-MB-231 cancer cell invasion potential and matrix metalloproteinases activity (MMP-2 and MMP-9) in breast cancer cell lines, MDA-MB-231 and MCF7. MTS cytotoxicity assay was used to evaluate the cytotoxic effect of the extract against the two tumour cell lines. Transwell invasion assay was used to investigate the invasive activity of MDA-MB-231 cancer cell line and gelatin zymography was used to determine the effect of C. roseus extract on the activity of MMP-2 and MMP-9 on the two tumour cell lines. The result showed that C. roseus extract was found to be not cytotoxic for both tumor cell line, MDA-MB-231 and MCF-7, with IC50 values more than 200µg/ml. However the extract showed significant inhibitory effect on MDA-MB-231 invasion ability (p<0.001), and suppressed the MMP-2 and MMP-9 activity on both tumour cell lines. In conclusion, our findings show C. roseus as a promising therapeutic candidate that inhibits invasive ability of breast cancer through modulating MMP-2 and MMP-9 activity and could potentially suppress the progression of breast cancer

References

Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E. and Forman, D. 2011. Global Cancer Statistics. CA Cancer Journal for Clinicians. 61(2): 69-90.

Weigelt, B., Peterse, J. L. and Van't Veer, L. J. 2005. Breast Cancer Metastasis: Markers and Models. Nature Reviews Cancer. 5(8): 591-602.

Hunter, K. W., Crawford, N. P. and Alsarraj, J. 2008. Mechanisms of Metastasis. Breast Cancer Research. 10(1): 1.

Talmadge, J. E. and Fidler, I. J. 2010. AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective. Cancer Research. 70 (14): 5649-5669.

Li, D. M. and Feng, Y. M. 2011. Signaling Mechanism of Cell Adhesion Molecules in Breast Cancer Metastasis: Potential Therapeutic Targets. Breast Cancer Research and Treatment. 128(1): 7-21.

Mego, M., Mani, S. A. and Cristofanilli, M. 2010. Molecular Mechanisms of Metastasis in Breast Cancer – Clinical Applications. Nature Reviews Clinical Oncology. 7 (12): 693-701.

Dano, K., Behrendt, N., Hoyer-Hansen, G., Johnsen, M., Lund, L. R., Ploug, M. and Romer, J. 2005. Plasminogen Activation and Cancer. Thromb Haemost. 93 (4): 676-681.

Egeblad, M. and Werb, Z. 2002. New Functions for The Matrix Metalloproteinases in Cancer Progression. Nature Reviews Cancer. 2(3): 161-174.

Rose, P., Huang, Q., Ong, C. N. and Whiteman, M. 2005. Broccoli and Watercress Suppress Matrix Metalloproteinase-9 Activity and Invasiveness of Human MDA-MB-231 Breast Cancer Cells. Toxicology and Applied Pharmacology. 209(2): 105–113.

Fang, J., Shing, Y., Wiederschain, D., Yan, L., Butterfield, C., Jackson, G. and Moses, M. A. 2000. Matrix Metalloproteinase-2 is Required for The Switch to The Angiogenic Phenotype in a Tumor Model. Proceedings of The National Academy of Sciences. 97(8): 3884-3889.

Xu, D., McKee, C. M., Cao, Y., Ding, Y., Kessler, B. M. and Muschel, R. J. 2010. Matrix Metalloproteinase-9 Regulates Tumor Cell Invasion Through Cleavage of Protease Nexin-1. Cancer Research. 70(17): 6988-6998.

Reuben, S. C., Gopalan, A., Petit, D. M. and Bishayee, A. 2012. Modulation of Angiogenesis by Dietary Phytoconstituents in The Prevention and Intervention of Breast Cancer. Molecular Nutrition & Food Research. 56(1): 14–29.

Loh, K. Y. 2008. Know the Medicinal Herb: Catharanthus roseus (Vinca rosea). Malaysian Family Physician. 3 (2): 123.

Wiart, C. 2002. Medicinal Plant of Southeast Asia. Selangor: Prentice Hall. 224-225.

Sain, M. and Sharma, V. 2013. Catharanthus roseus (An Anti-Cancerous Drug Yielding Plant) - A Review of Potential Therapeutic Properties. International Journal of Pure & Applied Bioscience. 1(6): 139-142.

Wong, S. K., Lim, Y. Y., Abdullah, N. R. and Nordin, F. J. 2011. Antiproliferative and Phytochemical Analyses of Leaf Extracts of Ten Apocynaceae Species. Pharmacognosy Research. 3(2): 100–106.

Wiart, C. 2006. Medicinal Plants of the Asia-Pacific: Drugs for the Future?. India: World Scientific.

Hsu, Y. L., Chen, C. Y., Lin, I. P., Tsai, E. M. and Kuo, P. L. 2012. 4-Shogaol, An Active Constituent of Dietary Ginger, Inhibits Metastasis of MDA-MB-231 Human Breast Adenocarcinoma Cells by Decreasing the Repression of NF-kappaB/Snail on RKIP. Journal of Agricultural and Food Chemistry. 60 (3): 852–861.

Hsu, Y. L., Wu, L. Y., Hou, M. F., Tsai, E. M. and Lee, J. N. 2011. Glabridin, An Isoflavan from Licorice Root, Inhibits Migration, Invasion and Angiogenesis of MDA-MB-231 Human Breast Adenocarcinoma Cells by Inhibiting Focal Adhesion kinase/Rho Signaling Pathway. Molecular Nutrition & Food Research. 55 (2): 318–327.

Brenton, J. D., Carey, L. A., Ahmed, A. A. and Caldas, C. 2005. Molecular Classification and Molecular Forecasting of Breast Cancer: Ready for Clinical Application. Journal of Clinical Oncology. 23 (29): 7350–7360.

Mao, L., Yuan, L., Slakey, L. M., Jones, F. E., Burow, M. E. and Hill, S. M. 2010. Inhibition of Breast Cancer Cell Invasion by Melatonin is Mediated Through Regulation of the p38 Mitogen-Activated Protein Kinase Signaling Pathway. Breast Cancer Research. 12(6): 1.

Nho, K. J., Chun, J. M., Lee, A. Y. and Kim, H. K. 2015. Anti-Metastatic Effects of Rheum Palmatum L. Extract in Human MDA-MB-231 Breast Cancer Cells. Environmental Toxicology and Pharmacology. 40(1): 30-38.

Adams, L. S., Phung, S., Yee, N., Seeram, N. P. and Li, L. 2010. Blueberry Phytochemicals Inhibit Growth and Metastatic Potential of MDA-MB-231 Breast Cancer Cells Through Modulation of The Phosphatidylinositol 3-kinase Pathway. Cancer Research. 70(9): 3594–3605.

Gu, Y-H. and Leonard, J. 2006. In Vitro Effects on Proliferation, Apoptosis and Colony Inhibition in ER-Dependent and ER- Independent Human Breast Cancer Cells by Selected Mushroom Species. Oncology Reports. 15(2): 417-423.

Huang, X., Xu, D., Wang, L. and Gao, L. 2004. Expression of MMP-2 and MMP-9 in The Tissues of Breast Carcinoma and its Relationship with Tumor Invasion and Metastasis. Chinese Journal of Clinical Rehabilitation. 8, 2190-2192.

Stamenkovic, I. 2003. Extracellular Matrix Remodelling: The Role of Matrix Metalloproteinases. The Journal of Pathology. 200(4): 448-464.

Artacho-Cordón, F., Ríos-Arrabal, S., Lara, P., Artacho-Cordón, A., Calvente, I. and Núñez, M. 2012. Matrix Metalloproteinases: Potential Therapy to Prevent The Development of Second Malignancies After Breast Radiotherapy. Surgical Oncology. 21(3): 143-151.

Wang, X.-F., Du, J., Zhang, T.-L., Zhou, Q.-M., Lu, Y.-Y., Zhang, H., and Su, S.-B. 2013. Inhibitory Effects of PC-SPESII Herbal Extract on Human Breast Cancer Metastasis. Evidence-Based Complementary and Alternative Medicine.

Wang, G. K. and Zhang, W. 2005. The Signaling Network of Tumor Invasion. Histology and Histopathology. 20: 593-602.

Reddy, K. B., Nabha, S. M. and Atanaskova, N. 2003. Role of MAP Kinase in Tumor Progression and Invasion. Cancer and Metastasis Reviews. 22(4): 395-403.

He, L., Yang, L., Tan, R., Zhao, S. and Hu, Z. 2011. Enhancement of Vindoline Production in Suspension Culture of The Catharanthus roseus Cell Line C20hi by Light and Methyl Jasmonate Elicitation. Analytical Sciences. 27(12): 1243.

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Published

2016-11-27

How to Cite

ANTI-INVASIVE EFFECT OF Catharanthus roseus EXTRACT ON HIGHLY METASTATIC HUMAN BREAST CANCER MDA-MB-231 CELLS. (2016). Jurnal Teknologi, 78(11-3). https://doi.org/10.11113/jt.v78.9870