Cytotoxic and Antimetastasis Effect of Ethyl Acetate Fraction from Caesalpinia sappan L. on MCF-7/HER2 Cells

Riris Istighfari Jenie, Sri Handayani, Ratna Asmah Susidarti, Zalinar Udin, Edy Meiyanto

Abstract


Overexpression of HER2 in breast cancer cell is found on invasive breast cancer and correlated with worse prognosis. Caesalpinia sappan L shows cytotoxic activity on various cancer cells. The goal of this research is to determine the cytotoxic activity and inhibition of migration and invasion of ethyl acetate fraction of Caesalpinia sappan L. (FEA) on HER2 overexpression-breast cancer cells (MCF-7/HER2). The MTT and flow cytometry assay showed that FEA revealed cytotoxic effect in a dose-dependent manner (IC50= 34 ± 3.1 µg/ml) and induced apoptosis, S and G2/M phase accumulation. Wound healing assay, gelatin zymography and immunoblotting assay showed that FEA inhibited migration and suppressed MMP2, MMP9, HER2 and Rac1 protein level. Thus, ethyl acetate fraction of Caesalpinia sappan L. is potential to be developed on future research especially to treat metastatic breast cancer with HER2 overexpression.

Keywords: Ethyl acetate fraction of Caesalpinia sappan L, cytotoxic effect, migration and invasion, MCF-7/HER2 cells


Full Text:

PDF

References


Brix, D.M., Bundgaard Clemmensen, K.K., Kallunki, T., 2014, When Good Turns Bad: Regulation of Invasion and Metastasis by ErbB2 Receptor Tyrosine Kinase, Cells 3, 53–78. doi:10.3390/cells3010053.

Brooks, S.A., Lomax-Browne, H.J., Carter, T.M., Kinch, C.E., Hall, D.M.S., 2010, Molecular interactions in cancer cell metastasis, Acta Histochem. 112, 3–25. doi:10.1016/j.acthis.2008.11.022.

Chen, Q.-Y., Xu, L.-Q., Jiao, D.-M., Yao, Q.-H., Wang, Y.-Y., Hu, H.-Z., Wu, Y.-Q., Song, J., Yan, J., Wu, L.-J., 2011. Silencing of Rac1 modifies lung cancer cell migration, invasion and actin cytoskeleton rearrangements and enhances chemosensitivity to antitumor drugs, Int. J. Mol. Med. 28, 769–776. doi:10.3892/ijmm.2011.775.

Hsieh, C.-Y., Tsai, P.-C., Chu, C.-L., Chang, F.-R., Chang, L.-S., Wu, Y.-C., Lin, S.-R., 2013, Brazilein suppresses migration and invasion of MDA-MB-231 breast cancer cells. Chem. Biol. Interact. 204, 105–115. doi:10.1016/j.cbi.2013.05.005.

Johnson, E., Seachrist, D.D., DeLeon-Rodriguez, C.M., Lozada, K.L., Miedler, J., Abdul-Karim, F.W., Keri, R.A., 2010., HER2/ErbB2-induced breast cancer cell migration and invasion require p120 catenin activation of Rac1 and Cdc42, J. Biol. Chem. 285, 29491–29501. doi:10.1074/jbc.M110.136770.

Kim, B., Kim, S.-H., Jeong, S.-J., Sohn, E.J., Jung, J.H., Lee, M.H., Kim, S.-H., 2012, Brazilin induces apoptosis and G2/M arrest via inactivation of histone deacetylase in multiple myeloma U266 Cells, J. Agric. Food Chem. 60, 9882–9889. doi:10.1021/jf302527p.

Kim, B.S., 2010, Brazilin inhibits of TPA-induced MMP-9 expression via the suppression of NF-κB activation in MCF-7 human breast carcinoma cells, J. Food Hyg. Saf.

Kim, E.-C., Hwang, Y.-S., Lee, H.-J., Lee, S.-K., Park, M.-H., Jeon, B.-H., Jeon, C.-D., Lee, S.-K., Yu, H.-H., You, Y.-O., 2005, Caesalpinia sappan induces cell death by increasing the expression of p53 and p21WAF1/CIP1 in head and neck cancer cells. Am. J. Chin. Med. 33, 405–414. doi:10.1142/S0192415X05003016.

Laksmiani, N.P.L., Susidarti, R.A., Meiyanto, E., 2015, Brazilein increases the sensitivity of doxorubicin on MCF-7 resistant doxorubicin (MCF-7/DOX) cells through inhibition of HER-2 activation. Int. J. Pharm. Pharm. Sci. 7.

Merkhofer, E.C., Cogswell, P., Baldwin, A.S., 2010, Her2 activates NF-kappaB and induces invasion through the canonical pathway involving IKKalpha. Oncogene 29, 1238–1248. doi:10.1038/onc.2009.410.

Nirmal, N.P., Rajput, M.S., Prasad, R.G.S.V., Ahmad, M., 2015, Brazilin from Caesalpinia sappan heartwood and its pharmacological activities: A review, Asian Pac. J. Trop. Med. 8, 421–430. doi:10.1016/j.apjtm.2015.05.014.

Nurzijah, Ika, Putri, D.D.P., Rivanti, E., Meiyanto, E., 2012, Secang (Caesalpinia sappan L.) heartwood ethanolic extract shows activity as doxorubicin co-chemotherapeutic agent by apoptosis induction on T47D breast cancer cells : View Article. Indones. J. Cancer Chemoprevention 3, 377–384.

Ridley, A.J., 2015, Rho GTPase signalling in cell migration. Curr. Opin. Cell Biol., Cell adhesion and migration 36, 103–112. doi:10.1016/j.ceb.2015.08.005.

Tao, L., Li, J., Zhang, J., 2013, Brazilein, a compound isolated from Caesalpinia sappan Linn., induced growth inhibition in breast cancer cells via involvement of GSK-3β/β-Catenin/cyclin D1 pathway. Chem. Biol. Interact. 206, 1–5. doi:10.1016/j.cbi.2013.07.015.

Tao, L., Li, J., Zhang, J., 2011, Brazilein Induced Cells Apoptosis in Human Breast Cancer MCF-7 Cells and Its Action Mechanism. J. Sun Yat-Sen Univ. Med. Sci. 32, 449–453.


Refbacks

  • There are currently no refbacks.