Oyster Mushroom (Pleurotus ostreatus) Inhibits Migration and Metastasis on 4T1 Breast Cancer Cells

Lodyta Nawang Tika, Layung Sekar Sih Wikanthi, Shofa Annur, Retno Murwanti

Abstract


Metastasis is the main cause of death among brast cancer patient. Pleorotus ostreatus is known as anticancer agent that inhibits angiogenesis. Ethanolic extract of Pleorotus ostreatus (EEP) which contains lovastatin is predicted to inhibit metastatic cancer through inhibition of MMP-2 and MMP-9. The aim of this study was to determined antiproliferative and anti metastatic activity of EEPw (Ethanolic extract of wet Pleorotus ostreatus) and EEPd (Ethanolic extract of dried Pleorotus ostreatus ) in 4T1 metastatic breast cancer cells line. Qualitative analysis of lovastatin was determined by thin layer chromatography (TLC) using dicloromethan and etil acetat as mobile phase and lovastatin standard. Scratch wound healing assay was used to determine migration inhition ability of EEP while MMP-9 and MMP-2 activity were analysed by gelatine zymography. Molecular docking was performed to know the interaction between lovastatin and MMP-2 & MMP-9. The result showed that EEPw and EEPd contain lovastatin which were proved by spray reaction with anisaldehid. Each of EEPw and EPPd had cytotoxic activity with IC50 760 and 400 μg/mL respectively. Both of them inhibited closure for about 50 % on 4T1 metastatic breast cancer cells line compared to control. Either EEPw or EEPd decreased MMP-9 expression level compared to control. Lovastatin had higher affinity to bond with either MMP-2 or MMP-9 than native ligand. Overall, EEP could be developed as anticancer agent which was targeted on MMP-2 and MMP-9.

Keywords : Pleurotus ostreatus, 4T1 metastatic cells, MMP-2, MMP-2, antimetastatic


Full Text:

PDF

References


Alarcón,J., Aguila, S., Arancibia-Avila, P., Fuentes, O., Zamorano-Ponce, E. and Hernández M., 2002, Production and Purification of Statins from Pleurotus ostreatus (Basidiomycetes) Strains., Z. Naturforsch C., 58(1-2),62-4. Link

Brooks, S.A, Lomax-Browne, H.J., Carter, T.M., Kinch, C.E. and Hall, D.M., 2010, Molecular Interaction in Cancer Cell Metastasis, Acta Histochem., 112(1), 3-25. CrossRef

Green, M. and Riana, V., 2008, Epidemiology Screening and Diagnosis of Breast Cancer in the Asia-Pasific Region: Current Perspectives and Important Consideration, Asia Pac. J. Clin. Oncol., 4(S3),S5-S13. CrossRef

Herndndez, D., Sanchez, J.E. and Yamasaki, K., 2003, A Simple Procedure for Preparing Substrate for P. Ostreatus Cultivation, Bioresour. Technol., 90(2),145-150. https://Link

Kalmis, E., Azbar, N., Yildiz, H. and Kalyoncu, F., 2008, Feasibility of Using Olive Mill Effluent (OME) as a Wetting Agent During the Cultivation of Oyster Mushroom, Pleurotus ostreatus on Wheat Straw, Bioresour. Technol., 99(1),164-169. CrossRef

Lakshmanan, D. and Radha, K.V., 2012, Production of Lovastatin from Pleurotus ostreatus and Comparison with Commercial Tablets, Int. J. Pharm. Pharm. Sci., 2(3), 53-56. Link

Liotta, L.A., Steeg, P.S. and Stetler-Stevenson, W.G., 1991, Cancer Metastasis and Angiogenesis: an Imbalance of Possitive and Negative Regulation, Cell, 64(2), 327-336. Link

Ramirez, A., Clavijo, C., Palanisamy, M., Soler-Rivas, C., Rodriguez, A., Francisco, M.M., et al., 2011, Edible Mushrooms as Potensial Sources of New Hypocholesterolemic Compound, International Conference on Mushroom Biology and Mushroom Products. Link

Ramírez-Anguiano, A.C., Santoyo, S., Reglero, G. and Soler-Rivas, C., 2007, Radical Scavenging Activities, Endogenous Oxidative Enzymes and Total Phenols in Edible Mushrooms Commonly Consumed in Europe, J. Sci. Food Agric., 87(12), 2272-2278. CrossRef

Rivilis, I., Milkiewicz, M., Boyd, P., Goldstein, J., Brown, M.D., Egginton, S., et al., 2002, Differential Involvement of MMP-2 and VEGF During Muscle Stretch - versus Shear Stress-induced Angiogenesis, Am. J. Physiol. Heart Circ. Physiol., 283(4), H1430-H1438. CrossRef

Stelter-Stevenson, W.G., 1994, Progegelatinase A Activation During Tumour Cell Invasion, Invasion Metastasis, 14(1-6), 259-268. Link

Toth M, Fridman R. 2011. Assessment of gelatinases (MMP-2 and MMP-9) by Gelatin Zymography, Methods Mol. Med.,57,163-174. CrossRef

WHO, 2014, WHO | Cancer’ WHO, Link, cited August, 19, 2014.

Wilhelm, S.M., Collier, I.E., Marmer, B.L., Eisen, A.Z., Grant, G.A. and Goldberg, G.I., 1989, SV40-Transformed Human Lung Fibroblasts Secrete a 92-kDa type IV Collagenase Which is Idential to That Secreted by Normal Human Macrophage, J. Biol. Chem., 264(29), 17213-17321. Link

Wong, W.W., Dimitroulakos, J., Minden, M.D. and Penn, L.Z., 2002, HMG-CoA Reductase Inhibitors and The Malignant Cell: the Statin Family of Drugs as Triggers of Tumor-Specific Apoptosis, Leukemia, 16(4), 508–519. CrossRef

Wu, J., Wong, W.W., Khosravi, F., Minden, M.D. and Penn, L.Z., 2004, Blocking the Raf/MEK/ERK Pathway Sensitizes Acute Myelogenous Leukemia Cells to Lovastatin-induced Apoptosis, Cancer Res., 64(18),6461–6468. CrossRef

Xioa, Y., Li, Y., Han, J., Pan, Y., Tie, L. and Li, X., 2012, Transgelin 2 Participates in Lovastatin-Induced- Anti-angiogenic Effectc in Endhothelial Through a Phorphorylated Myosin Light Chain-Related Mechanism, PloS One, 7(10), e46510. CrossRef

Zhao, T.T., Trinh, D., Addison, C.L. and Dimitroulako, J., 2010, Lovastatin Inhibits VEGFR and AKT Synergisitic Cytotoxity in Combination with VEGFR Inhibitor, PloS One, 5(9), e12563. CrossRef




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev7iss3pp99-103

Copyright (c) 2017 Indonesian Journal of Cancer Chemoprevention

Indexed by:

               

               

      

 

Indonesian Society for Cancer Chemoprevention