Doxorubicin Induces Lamellipodia Formation and Cell Migration
Abstract
Breast cancer is the main cause of cancer death among women, especially breast cancer metastasis. Metastasis process begins with the ability of cell cancer invasion. Doxorubicin, a antracycline chemotheraphy, is known to induce TGFβ1, thus promote invasion. The aim of this study is to optimize doxorubicin doses to induce lamellipodia formation in 4T1 and MCF-7/HER2 cells. Lamellipodia formation was observed by morphological changes using microscope inverted. The effect of doxorubicin on cell viability was analyzed using MTT assay. Rac1 expression after doxorubicin exposure was determined by western blotting. Lamellipodia formation was observed by morphological change of the cell at the dose 10, 25, 50 and 100 nM. Doxorubicin at the dose of 10 nM could induced lamellipodia formation without affect cell viability in both 4T1 and MCF-7/HER2 cells. Doxorubicin induced cell cycle arrest at G2/M phase at all doses. Doxorubicin 10 nM also decrease Rac1 expression compared to control.
Key words: Doxorubicin, lamellipodia, Rac1, migration.
Full Text:
PDFReferences
Arpaia, E., Blaser, H., Quintela-Fandino, M., Duncan, G., Leong, H.S., Ablack, A., et al., 2012, The Interaction Between Caveolin-1 and Rho-GTPases Promotes Metastasis by Controlling the Expression of Alpha5-integrin and the Activation of Src, Ras and Erk, Oncogene, 31(7), 884-896. CrossRef
Bandyopadhyay, A., Wang, L., Agyin, J., Tang, Y., Lin, S., Yeh, I.-T., et al., 2010, Doxorubicin in Combination with a Small TGFβ Inhibitor: A Potential Novel Therapy for Metastatic Breast Cancer in Mouse Models, PLoS ONE, 5(4), e10365. CrossRef
Ehrlich, J.S., Hansen, M.D.H. and Nelson, W.J., 2002. Spatio-Temporal Regulation of Rac1 Localization and Lamellipodia Dynamics during Epithelial Cell-Cell Adhesion, Dev. Cell, 3(2), 259–270. CrossRef
Febriansah, R., Dyaningtyas, D.P.P., Sarmoko, Nurulita, N.A., Meiyanto, E. and Nugroho, A.E., 2014, Hesperidin as a Preventive Resistance Agent in MCF–7 Breast Cancer Cells Line Resistance to Doxorubicin, Asian Pac. J. Trop. Biomed., 4(3), 228–233. CrossRef
Hermawan, A., Meiyanto, E. and Susidarti, R.., 2010, Hesperidine Increases Cytotoxic Effect of Doxorubicin on MCF-7 Cells, Indones. J. Pharm., 21(1), 8–17. CrossRef
Hermawan, A., Nur, K.A., Sarmoko, Dewi, D., Putri, P. and Meiyanto, E., 2012, Ehanolic Extract of Moringa oleifera Increased Cytotoxic Effect of Doxorubicin on Hela Cancer Cells, Journal of Natural Remedies, 12(2), 108-114. Link
Mosmann, T., 1983, Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays, J. Immunol. Methods., 65(1-2), 55–63. CrossRef
Putri, H., Jenie, R.I., Handayani, S., Kastian, R.F. and Meiyanto, E., 2016, Combination of Potassium Pentagamavunon-0 and Doxorubicin Induces Apoptosis and Cell Cycle Arrest and Inhibits Metastasis in Breast Cancer Cells, Asian Pac. J. Cancer Prev., 17(5), 2683–2688. CrossRef
Rowan T. Chlebowski., 1979, Adriamycin (Doxorubicin) Cardiotoxicity: A Review, West J. Med., 131(5), 364-368. Link
Spaargaren, M. and Bos, J.L., 1999, Rab5 Induces Rac-independent lamellipodia Formation and Ccell Migration, Mol. Biol. Cell, 10(10), 3239–3250. CrossRef
Steffen, A., Ladwein, M., Dimchev, G.A., Hein, A., Schwenkmezger, L., Arens, S., et al., 2013, Rac Function is Crucial for Cell Migration but is not Required for Spreading and Focal Adhesion Formation, J. Cell Sci., 126(20),4572-4588. CrossRef
Xu, J., Lamouille, S. and Derynck, R., 2009, TGF-β-Induced Epithelial to Mesenchymal Transition, Cell Res., 19, 156–172. CrossRef
DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev8iss2pp61-67
Copyright (c) 2017 Indonesian Journal of Cancer Chemoprevention
Indexed by:
Indonesian Society for Cancer Chemoprevention
