Secang (Caesalpinia sappan L.) Heartwood Ethanolic Extract Shows Activity as Doxorubicin Co-chemotherapeutic Agent by Apoptotis Induction on T47D Breast Cancer Cells

Ika Nurzijah, Dyaningtyas Dewi Pamungkas Putri, Erlina Rivanti, Edy Meiyanto

Abstract


Doxorubicin, primary chemoteurapeutic agent used for breast cancer treatment, is known to have various side effects included multi drug resistance (MDR) phenomenon. Therefore, exploration of co-chemotherapeutic agent is important to be conducted in order to prevent MDR. Secang (Caesalpinia sappan L.) which contains active compounds brazilin and brazilein, is proven to have activity as anticancer. The aim of this study is to determine the potency of Caesalpinia sappan L. ethanolic extract (CEE) as co-chemotherapeutic agent of doxorubicin and its mechanism through apoptosis induction on T47D breast cancer cells. Caesalpinia sappan L. heartwood powder was macerated with ethanol 70%. The cytotoxic effect of CEE alone and its combination with doxorubicin was analyzed using MTT assay. Apoptosis assay was done by flowcytometry-annexin V method. CEE showed cytotoxic activity on T47D cells with IC50 value of 35 µg/ml, while combinatorial test showed that all of combination doses of CEE and doxorubicin gave synergistic effect. Flowcytometry-annexin V assay proved that treatment of CEE induced apoptosis of doxorubicin. Based on these results, we conclude that Caesalpinia sappan L. heartwood ethanolic extract is potential to be developed as co-chemotherapeutic agent of doxorubicin.

Keywords : Caesalpinia sappan L., doxorubicin, apoptosis, T47D cells


Full Text:

PDF

References


Bouker, K.B., Skaar, T.D., Riggins, R.B., Harburger, D.S., Fernandez, D.R., et al., 2005, Interferon Regulatory Factor-1 (IRF-1) Exhibits Tumor Supressor Activities in Breast Cancer Associated with Caspase Avtivation and Induction of Apoptosis, Carcinogenesis, 26(9), 1527-1535. CrossRef

Dinkes, 2010, Sistem Informasi Rumah Sakit (SIRS) Provinsi D.I.Y Yogyakarta, Dinkes D.I.Y Yogyakarta.

Dong, J.T, 2006, Prevalent Mutations in Prostate Cancer, J. Cell Biochem., 97 (3), 433-447. CrossRef

Fang, L., Barekati, Z., Zhang, B., Liu, Z. and Zhong, X., 2011, Targeted Therapy in Breast Cancer: What’s New?, Swiss Med. Wkly., 141, 13231. CrossRef

Fitriasari, A., Junedi, S., Hermawan, A., Susidarti, R.A. and Meiyanto, E., 2009, Induction of Apoptosis and Cell Cycle Arrest by Naringenin to Increase The Cytotoxic Activity of Doxorubicin on Breast Cancer Cell Lines, In Risalah The International Conference on Pharmacy and Advance Pharmaceutical Science 2009, Yogyakarta, 124.

Gunawan, S.G., 2007, Farmakologi dan Terapi, 5th Edition, Jakarta: Bagian Farmakologi Fakultas Kedokteran Universitas Indonesia.

Hanahan, D. and Weinberg, R.A., 2011, Hallmarks of Cancer : The Next Generation, Cell, 144(5), 646-675. CrossRef

Keane, M.M., Ettenberg, S.A., Nau, M.M., Russell, E.K. and Lipkowitz, S., 1999, Chemotherapy Augments TRAIL-induced Apoptosis in Breast Cell Lines, Cancer Res., 59, 734-741. Link

Kim, E.C., Hwang, Y.S., Lee, H.J., Lee, S.K., Park, M.H., Jeon, B.H., et al., 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(3), 405-14. CrossRef

Lee, C.H., 2010, Reserving Agents for ATP-Binding Cassette Drug Transporters, Methods Mol. Biol., 596, 325-340. CrossRef

Nurulita, N.A. and Muflih, Y.A., 2006, Efek Sitotoksik Ekstrak Metanol Kayu Secang (Caesalpinia sappan L.) pada Sel Kanker Payudara T47D melalui Induksi Apoptosis, PHARMACY, 4(1), 1-9.

Potter, A.J., Gollahon K.A., Palanca B.J.A., Harbert M.J., Choi Y.M., Moskovitz A.H., et al., 2002, Flow Cytometric Analysis of The Cell Cycle Phase Specificity of DNA Damage Induced by Radiation, Hydrogen Peroxyde and Doxorubicin, Carcinogenesis, 23(3), 389-401. Link

Ren, L., Yang, X., Wang, G., Zhang, H., Zhao, L. and Mi, Z., 2011, Inhibition Effect of Brazilin to Human Bladder Cancer Cell Line T24, World Acad. Sci. Eng. Technol., 5(12), 567-661. Link

Schafer, J.M., Lee, E.S., O’Regan, R.M., Yao, K. and Jordan, V.C., 2000, Rapid Development of Tamoxifen-stimulated Mutant p53 Breast Tumors (T47D) in Athymic Mice, Clin. Cancer Res., 6(11), 4373-4380. Link

Staerk, D., Lykkeberg, A.K., Christensen, J., Budnik, B.A., Abe, F. and Jaroszewski, J.W., 2002, In Vitro Cytotoxic Activity of Phenanthroindolizidine Alkaloids from Cynanchum vincetoxicum and Tylophora tanakae against Drug-Sensitive and Multidrug Resistant Cancer Cells, J. Natural Prod., 65(9), 1299-1302. Link

Tao, L., Li , J. and Zhang, J, 2011, Brazilein Overcame ABCB1-Mediated Multidrug Resistance in Human Leukaemia K562/AO2 Cells, Afr. J. Pharm. Pharmacol., 5(16), 1937-1944. CrossRef

Wang,S.L., Cai, B., Cui, C.B., Zhang, H.F., Yao, X.S., and Qu, G.X., 2001, Apoptosis induced by Caesalpinia sappan L. extract in leukemia cell line K562, Chinese J. Cancer, 20(12), 1376-1379. Link

Wattanapitayakul, S.K., Chularojmontri, L., Herunsalee, A., Charuchongkolwongse, S., Niumsakul, S. and Bauer, J.A., 2005, Screening of Antioxidants from Medicinal Plants for Cardioprotective Effect against Doxorubicin Toxicity, Basic Clin. Pharmacol. Toxicol., 96(1), 80-87. CrossRef

Wong,R.S., 2011, Apoptosis in Cancer: from Pathogenesis to Treatment, J. Exp. Clin. Cancer Res., 30, 87. CrossRef

Zhang, H., Piao, J.H., Ren, LS., Tang,Y., and Tian, F, 2002, A study on aqueous extract of lignum sappan inducing HL-60 cell apoptosis. Chinese Remedies & Clinics, 2(1), 16-17.

Zhong, X., Wu,B., Pan, Y.J. and Zheng, S., 2009, Brazilein Inhibits Survivin Protein and mRNA Expression and Induces Apoptosis in Hepatocellular Carcinoma HepG2 cells, Neoplasma, 56(5), 387-392. Link




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev3iss2pp376-383

Copyright (c) 2017 Indonesian Journal of Cancer Chemoprevention

Indexed by:

               

               

      

 

Indonesian Society for Cancer Chemoprevention