Secang Heartwood Ethanolic Extract (Caesalpinia sappan L.) Inhibits Mesenchymal Stem Cells Senescence

Asri Mega Putri, Nindya Budiana Putri, Rahmawaty Rachmady, Idlohatud Dilalah, Retno Murwanti, Edy Meiyanto


Antioxidants have the ability to scavenge free radicals, leading to inhibition of cells senescence. Secang Heartwood (Caesalpinia sappan L.) contains flavonoid brazilein, known of its high antioxidant activity. However, the activity of secang as senescent cells inhibitor has not been known. The aim of this study is to explore the potential of Caesalpinia sappan ethanolic extract (CSE) as free radical scavenger, thus inhibits senescent cells. Two concentrations of SE under IC50, 2µg/mL, 5µg/mL and 10µg/mL were applied on Mesenchymal Stem Cells (MSCs) and combined with 5µM of doxorubicin (Dox) as senescence inductor; both of them were compared with MSCs-Dox group. X-gal, chromogenic substrate of senescent cells, was given on MSCs, giving blue stain on senescent cells. To explore brazilein mechanism in senescence inhibition, molecular docking using PLANTS on topoisomerase II was performed. MSCs that treated with 10µg/mL of SE qualitatively showed reduction intensity of blue stain. Number of stained cells also reduced from 76% of MSCs-Dox to 38 % of 10µg/mL SE-Dox group. Docking score shows that brazilein (-86.91) is more stable to interact with topoisomerase II than doxorubicin (-82.46) and has same binding site (Val 174). These findings demonstrate starting knowledge on CSE potential as senescent cells inhibitor through brazilein activity on topoisomerase II.

Keyword: Caesalpinia sappan L., Senescence, β-galactosidase, Molecular Docking

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Becker, T.M. and Rizos, H., 2003, Regulation of Cellular Senescence by the Retinoblastoma Pathway. In: Kaul S.C. and Wadhwa R.,editor, Aging of Cells in and Outside the Body, Biology of Aging and its Modulation, Vol 2. Dordrecht: Springer. CrossRef

Bersenev, A., Cell therapy clinical trials in 2011,, Cited February 12, 2016.

Buttiglieri, S., Ruella, M., Risso, A., Spatola, T., Silengo, L., Avvedimento, E.V., et al., 2011, The Aging Effect of Chemotherapy on Cultured Human Stem Cells, Exp. Hem., 39(12), 1171-1181. CrossRef

Chainiaux, F. D., Jorge, D.E., Judith, C. and Oliver, T., 2009, Protocols to Detect Senescence-associated Beta-galactosidase (SA-βgal) Activity, A Biomarker of Senescent Cells in Culture and in vivo, Nat. Pub. Group, 4(12), 1798-1804. CrossRef

Cipriani, P., Di Benedetto, P., Liakouli, V., Del Papa, B., Di Padova, M., Di Ianni, M., et al., 2013. Mesenchymal Stem Cells (MSCs) from Scleroderma Patients (SSc) Preserve Their Immunomodulatory Properties Although Senescent and Normally Induce T Regulatory Cells (Tregs) with a Functional Phenotype: Implications for Cellular-based Therapy, Clin. Exp. Immunol., 173(2), 195-206. CrossRef

Collado, M., Blasco, M.A. and Serrano, M., 2007, Cellular Senescence in Cancer and Aging, Cell, 130(2), 223-233. CrossRef

Demidenko, Z.N. and Blagosklonny, M.V., 2008, Growth Stimulation Leads to Cellular Senescence When the Cell Cycle is Blocked, Cell Cycle, 7(21), 3355-3361. CrossRef

Departemen Kesehatan RI, 2010, Suplemen I Farmakope Herbal Indonesia, Jakarta: Departemen Kesehatan RI.

Dimri, G. P., Lee, X. and Basile, G., 1995., A Biomarker that Identifies Senescent Human Cells in Culture and in Aging Skin in vivo, Cell Biol., 92, 9363-9367.

Gewirtz, D.A., 1999, A Critical Evaluation of the Mechanisms of Action Proposed for the Antitumor Effects of the Anthracycline Antibiotics Adriamycin and Daunorubicin, Biochem. Pharmacol., 57(7), 727–741. CrossRef

Gewirtz, D.A., Holt, S.E. and Elmore, L.W., 200, Accelerated Senescence: An Emerging Role in Tumor Cell Response to Chemotherapy and Radiation, Biochem. Pharmacol., 76(8), 947-957. CrossRef

Hayflick, L., 1965, The Limited in vitro Lifetime of Human Diploid Cell Strains, Exp. Cell. Res., 37(3), 614-636. CrossRef

Heyne, K., 1987, Tumbuhan Berguna Indonesia. Jilid. II. Jakarta: Departemen Kehutanan Republik Indonesia.

Khamsita, R., Hermawan, A., Putri, D. 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), 444-449. CrossRef

Larsen, A.K., Escargueil, A.E. and Skladanowski, A., 2003, From DNA Damage to G2 Arrest: The Many Roles of Topoisomerase II, Prog. Cell Cycle Res. 5: 295–300.

Lawless, C., Wang, C., Jurk, D., Merz, A., von Zglinicki, T., Passos, J.F. 2010. Quantitative assessment of markers for cell senescence. Exp. Ger., 45(10), 772-778. CrossRef

Lim, D.K., Choi, U. and Shin, D.H., 1997, Antioxidative Activity of Some Solvent Extract from Caesalpinia sappan Linn, Korean J. Food Sci. Technol., 28(1), 77−82.

Meirelles, L.D.S. and Nardi, N.B, 2003, Murine Marrow-derived Mesenchymal Stem Cell: Isolation, in vitro Expansion, and Characterization, British J. Haem., 123(4), 702-711. CrossRef

Purnomo, H., 2011, Kimia Komputasi: Molecular Docking PLANTS, Yogyakarta: Pustaka Pelajar.

Rachmady, R., 2015, Aktivitas Sitotoksik Ekstrak Etanolik Kayu Secang (Caesalpinia sappan L.) terhadap Sel Kanker Payudara Bertarget Molekuler pada Reseptor HER-2, Essay, Universitas Gadjah Mada, Yogyakarta.

Shahidi, F., 1996, Natural Antioxidants: Chemistry, Health Effects, and Applications, Illionis: AOCS Press.

Shay, J.W., Wright, W.E. and Hayflick, L, 2000, His Limit and Cellular Aging, Nat. Rev. Mol. Cell Biol., 1(1), 72-76. CrossRef

Shlush, L.I., Itzkovitz, S., Cohen, A., Rutenberg, A., Berkovitz, R., Yehezkel, S., et al., 2011, Quantitative Digital in situ Senescence-associated b-galactosidase Assay, BMC Cell Biol., 12(1), 16. CrossRef

Van Epps, H.L., 2005, How SLPI (secretory leukocyte protease inhibitor) soothes, J. Exp. Med., 202, 12.

Wang, Q., Zambetti, G.P. and Suttle, D.P., 1997, Inhibition of DNA Topoisomerase IIa Gene Expressionby the p53 Tumor Suppressor, Mol. Cell Biol., 1, 389-397. CrossRef


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