Revealing the Potential of Compounds in Sappan Wood as Cervical Cancer Metastasis Chemopreventive Agent With MMP9 Target

Hanaan Emilia Adi Hastuti, Midori Rahmadhany Putri Adisusilo, Yusufia Asmarani Ashar, Edy Meiyanto, Riris Istighfari Jenie


Matrix metalloproteinase-9 (MMP9) has an essential role in cervical cancer metastasis. Sappan wood extract (SWE) from Caesalpinia sappan contains metabolites that have pharmacological effects and can potentially inhibit metastasis by targeting the protein markers. This research aims to discover the potency of compounds in C. sappan as chemopreventive agents for metastasis in cervical cancer by targeting MMP9. SWE was obtained by maceration with methanol and analyzed using thin layer chromatography (TLC). In vitro cytotoxicity test of SWE on HeLa cells was performed by direct counting method. MMP9 expression profiles and survival rates in cervical cancer patients were explored through bioinformatics studies by the GEPIA database. The CMAUP and PubChem databases were used to obtain the metabolomic profile of SWE. SWE compounds’ activities on target proteins were obtained through KNIME software, while its interaction with MMP9 was analyzed using molecular docking with MOE software. We obtained SWE with a yield of 9.7% w/w. The extract contains brazilin and is indicated by the spot appearance at Rf 0.375. The cytotoxicity of SWE against HeLa cells was considered potential as the IC50 value was 54.93 μg/mL. Based on the bioinformatics analysis, there is a significant difference in MMP9 expression between normal and cervical cancer tissue. The patient’s survival probability decreased if MMP9 was overexpressed. The molecular docking results showed that active compounds of SWE bind to the MMP9 inhibition site with higher affinity compared to the native ligand. This study reveals that SWE potential to be developed as a chemopreventive agent through metastasis inhibition in cervical cancer by targeting MMP9.

Keywords: Caesalpinia sappan L., metastasis, bioinformatics, molecular docking, MOE.

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American Cancer Society. 2020. About Cervical Cancer. Website,, accessed on June 27, 2021.

Deryugina, E.I., and Quigley, J.P., 2006, Matrix metalloproteinases and tumor metastasis, Cancer Metastasis Rev, 25(1), 9–34. CrossRef

Handayani, S., Susidarti, R.A., Udin, Z., Meiyanto, E., and Jenie, R.I., 2016, Brazilein in combination with cisplatin inhibit proliferation and migration on highly metastatic cancer cells, 4T1, Indones J Biotechnol, 21(1), 38-47. CrossRef

Handayani, S., Susidarti, R.A., Jenie, R.I., and Meiyanto, E., 2017, Two active compounds from Caesalpinia sappan L. in combination with cisplatin synergistically induce apoptosis and cell cycle arrest on WiDr cells, Advanced pharmaceutical bulletin, 7(3), 375. CrossRef

Handayani, S., Susidarti, R.A., Lotulung, P.D.N., Darmawan, A., Meiyanto, E., and Jenie, R.I., 2020, Antimigratory Activity of Brazilin-Containing Fraction from Caesalpinia sappan L. on MDAMB-231 Cells, HAYATI Journal of Biosciences, 27(4), 266-266.

Haryanti, S., Murwanti, R., Putri, H., Ilmawati, G.P.N., Pramono, S., and Meiyanto, E., 2017, Different 4T1 cells migration under Caesalpinia sappan L. and Ficus septica Burm. f ethanolic extracts, Indonesian Journal of Cancer Chemoprevention, 8(1), 21-26. CrossRef

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

Hung, T.M., Dang, N.H., and Dat, N.T., 2014, Methanol extract from Vietnamese Caesalpinia sappan induces apoptosis in HeLa cells, Biol Res., 47, 1–5. CrossRef

Jenie, R., Handayani, S., Susidarti, R.A., and Meiyanto, E., 2020, The Effect of Brazilin from Caesalpinia sappan on Cell Cycle and Modulation and Cell Senescence in T47D cells, Indonesian Journal of Pharmacy, 31(2), 84-91. CrossRef

Kim, B., Kim, S.H., Jeong, S.J., Sohn, E.J., Jung, J.H., Lee, M.H., and Kim, S.H., 2012, Brazilin induces apoptosis and G2/M arrest via inactivation of histone deacetylase in multiple myeloma U266 cells, Journal of agricultural and food chemistry., 60(39), 9882-9889. CrossRef

Ray, S., Koshy, N.R., Reddy, P.J., and Srivastava, S., 2012, Virtual Labs in proteomics: New E-learning tools, Journal of Proteomics., 75, 2515–2525. CrossRef

Shin, W.R., Um, H.J., Kim, Y.C., Kim, S.C., Cho, B.K., Ahn, J.Y., Min, J., and Kim, Y.H., 2021, Biochemical characterization and molecular docking analysis of novel esterases from Sphingobium chungbukense DJ77, International Journal of Biological Macromolecules., 168, 403-411. CrossRef

Tang, Z., Li, C., Kang, B., Gao, G., Li, C., and Zhang, Z., 2017, GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses, Nucleic acids research., 45(W1), W98-W102. CrossRef

Tao, L.Y., Li, J.Y., and Zhang, J.Y., 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, Chemico-biological interactions., 206(1), 1-5. CrossRef

Ueda, J.Y., Tezuka, Y., Banskota, A.H., Tran, Q.L., Tran, Q.K., Harimaya, Y., Saiki, I., and Kadota, S., 2002, Antiproliferative Activity of Vietnamese Medicinal Plants, Biol. Pharm. Bull., 25(6), 753-760. CrossRef

Sulistyawati, D., Faizah, Z., and Kurniawati, E.M., 2020, An Association Study of Cervical Cancer Correlated with The Age of Coitarche in Dr. Soetomo Hospital Surabaya, Indonesian Journal of Cancer., 14(1), 3-7. CrossRef

Weerapreeyakul, N., Nonpunya, A., Barusrux, S., Thitimetharoch, T., and Sripanidkulchai, B., 2012, Evaluation of the anticancer potential of six herbs against a hepatoma cell line, Chin. Med., 7, 15. CrossRef

Wright, T.C., and Kuhn, L., 2012, Alternative approaches to cervical cancer screening for developing countries, Best Pract Res Clin Obstet Gynaecol., 26, 197–208. CrossRef

Yousef, E.M., Tahir, M.R., St-Pierre, Y., and Gaboury, L.A., 2014, MMP9 expression varies according to molecular subtypes of breast cancer, BMC Cancer., 14,, 609. CrossRef


Copyright (c) 2022 Hanaan Emilia Adi Hastuti, Midori Rahmadhany Putri Adisusilo, Yusufia Asmarani Ashar, Riris Istighfari Jenie

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Indonesian Society for Cancer Chemoprevention