Antiproliferative Effect of Secang Heartwood Ethanolic Extract (Caesalpinia sappan L.) on HER2-Positive Breast Cancer Cells

Rahmawaty Rachmady, Laely Muntafiah, Fahmi Rosyadi, Imroatus Sholihah, Sri Handayani, Riris Istighfari Jenie


Human Epidermal Growth Factor Receptor 2 (HER2) plays critical role in the initiation of breast cancer cell proliferation. Inhibition of HER2 overexpression is a promising strategy in the treatment of breast cancer. One of the potential natural substances that possess cytotoxic in cancer cells is Secang (Caesalpinia sappan L.). Ethanolic extract of secang heartwood containing brazilein and brazilin shows cytotoxic effect on various cancer cells. Thus this research aims to determine the proliferative inhibition activity of secang heartwood ethanolic extract (SEE) through HER2 expression on MCF-7/HER2 positive. Cytotoxic activity of SEE on MCF-7/HER2 positive cells was observed by MTT assay, meanwhile the inhibition activity of  HER2 on MCF-7/HER2 cells was determined by immunofluoresence assay. Furthermore, to confirm the possible mechanism of brazilein and brazilin for its cytotoxic activity was studied through molecular docking using PLANTS software. Based on this study, SEE exhibited cytotoxic effect on MCF-7/HER2 positive cells with IC50 value of 25 µg/ml, and EES also inhibited HER2 expression, indicated that the antiproliferative effect of SEE was possible through the inhibition of HER2. Docking score of brazilein, brazilin, and native ligand on HER2 were -77; -73; -120 respectively, showed the affinity of brazilein in HER2 was lower than affinity of native ligand, but they had specific amino acid to interaction. Hence, SEE can be developed as one of promising chemopreventive agent from natural products.

Keywords: Caesalpinia sappan L., cytotoxic, immunofluorescence, molecular docking, MCF7/HER2 cells

Full Text:



Dolinsky, C, 2002, Breast Cancer: The Basic. Abramson Cancer Center of the University of Pennsylvania, taken from the site

Eccles, S.A. , 2001, C-erb2/HER2/neu in The Role of Breast Cancer Progression and Metastasis, J. Mammary Gland Biol. Neoplasia, 6 (4), 393-406. Link

Foster, J.S., Henley, D.C., Ahamed, S. and Wimalasena, J., 2001, Estrogens and Cell Cycle Regulation in Breast Cancer., Trends Endocrinol. Metab., 12 (7), 320-327. CrossRef

Gibbs, J.B., 2000, Anticancer Drug Targets: Growth Factor and Growth Factor Signaling, J. Clin. Invest., 105(1), 9-13. CrossRef

Hsieh, C.Y., Tsai, P.C., Chu, C.L., Chang, F.-R., Chang, L.S., Wu, Y.C., et al., 2013, Brazilein Suppresses Migration and Invasion of MDA-MB-231 Breast Cancer Cells, Chem. Biol. Interact., 204(2), 105–115. CrossRef

Khamsita, R., Hermawan, A.,, Putri, D. D. P. and Meiyanto, E. 2012. Ethanolic Extract of Secang (Caesalpinia sappan L.) Wood Performs as Chemosensitizing Agent Through Apoptotic Induction on Breast Cancer MCF-7 Cells, Indones. J. Cancer Chemoprevent.,3(3), 445-450. Link

Konkimalla, McCubrey, J.A. and Efferth, T., 2009, The Role of Downstream Signaling Pathways of the Epidermal Growth Factor Receptor for Artesunate’s Activity in Cancer Cells, Curr. Cancer Drug Targets., 9(1), 72–80. Link

Laksmiani, N., L., Susidarti, R., A. and Meiyanto, E., 2014, 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(2), 525-528. Link

Laskin, J.J. and Sandler, A.B., 2004, Epidermal Growth Factor Receptor: A Promising Target in Solid Tumors, Cancer Treat. Rev., 30, 1-17. CrossRef

Carey, L.A., Perou, C.M., Livasy, C.A., Dressler, L.G., Cowan, D., Conway, K., et al., 2006, Breast Cancer Subtypes, and Survival in the Carolina Breast Cancer Study, JAMA, 295(21), 2492 - 2502. CrossRef

Siddiqa, A., Long, L.M., Li, L., Marciniak, R.A. and Kazhdan, I., 2008, Expression of HER-2 in MCF-7 Breast Cancer Cells Modulates Anti-Apoptotic Reseptors Survivin and Bcl-2 via the Extracellular Signal-Related Kinase (ERK) and Phosphoinositide-3 Kinase (PI3K) Signalling Pathways, BMC Cancer, 8, 129. CrossRef

Yen, C.T., Nakagawa-Goto, K., Hwang, T.L., Wu, P.C., Morris-Natschke, S.L., Lai, W.C., et al., 2010, Antitumor Agents. 271. Total Synthesis and Evaluation of Brazilein and Analogs as Anti-inflammatory and Cytotoxic Agents, Bioorg. Med. Chem. Lett., 20(3), 1037-1039. CrossRef

Zhong, X., Wu, B., Pan, Y.J. and Zheng, S., 2009, Brazilein Inhibits Survivin Protein and mRNA Expression and induces apoptosis in HepG2 Hepatocellular Carcinoma Cells, Neoplasma, 56(5),387-92. CrossRef


Copyright (c) 2017 Indonesian Journal of Cancer Chemoprevention

Indexed by:




Indonesian Society for Cancer Chemoprevention