Efek Sinergis Kombinasi Ekstrak Etanolik Kayu Secang dan Rimpang Lempuyang pada Sel Kanker Payudara MCF-7

  • Sari Haryanti Balai Besar Penelitian dan Pengembangan Tanaman Obat dan Obat Tradisional
  • Ika Yanti M. Sholikhah
  • Yuli Widiyastuti
Keywords: Caesalpinia sappan L, Zingiber zerumbet L, Combination index


Cancer is one of critical, chronic, and complex disease, also becoming the high cause of death in the world. Brazilin and brazilein in sappan wood (Caesalpinia sappan L.) and zerumbone in bitter ginger rhizome (Zingiber zerumbet L.) are known having cytotoxic activity with different mechanisms. This study aimed to examine combination effect of sappan wood and bitter ginger rhizome. Sappan wood and bitter ginger rhizomes macerated with ethanol 96% for 3x24 hours, filtered, and evaporated to obtain dried extract.Cytotoxic effect on MCF-7 cells was done using MTT assay. Combination Index (CI) was determined by CompuSyn based on the result of cytotoxic combination. Cell cycle profile and apoptosis induction was analyzed by flow cytometry. Sappan wood extracts and bitter ginger rhizome exhibited cytotoxic effects on MCF-7 cells with the IC50 values of 30 and 155 μg/mL respectively. The combination of sappan wood 15 μg/mL and bitter ginger 8, 12, 24, and 60 μg/mL produced synergistic effect with the CI value of 0.57-0.85. Sappan wood 15 μg/mL combined with bitter ginger 8 and 24 μg/mL showed cell cycle inhibition at G2/M phase. The combination also increased apoptosis induction compared to untreated cells and its single treatment.The combination of sappan wood ethanolic extracts and bitter ginger rhizome showed synergistic cytotoxic effect. Its synergism effect revealed through cell cycle arrested at G2/M phase and acceleration of apoptotic induction.


Che CT, Wang ZJ, Chow MSS, Lam CWK. Herb-herb combination for therapeutic enhancement and advancement: Theory, practice and future perspectives. Molecules. 2013;18(5):5125–41.

Ghoncheh M, Mohammadian-hafshejani A, Salehiniya H. Incidence and mortality of breast cancer and their relationship to development in Asia. Asian Pac J Cancer Prev. 2015;16(14):6081–7.

Aung TN, Qu Z, Kortschak RD, Adelson DL. Understanding the effectiveness of natural compound mixtures in cancer through their molecular mode of action. Int J Mol Sci. 2017;18(3):1–20.

Nirmal NP, Rajput MS, Prasad RGS V, Ahmad M. Brazilin from Caesalpiniasappan heartwood and its pharmacological activities: {A} review. Asian Pac J Trop Med. 2015;8(6):421–30.

Haryanti S, Murwanti R, Putri H, Ilmawati GPN, Pramono S, Meiyanto E. Different 4T1 cells migration under Caesalpinia sappan L. and Ficus septica Burm.f ethanolic extracts. Indonesia J Cancer Chemoprevention. 2017 Feb;8(1):21–6.

Haryanti S, Pramono S, Murwanti R, Meiyanto E. The synergistic effect of doxorubicin and ethanolic extracts of Caesalpinia sappan L. wood and Ficus septica Burm.f. leaves on viability, cell cycle progression, and apoptosis induction of MCF ­ 7 cells. Indonesian Journal of Biotechnology. 2016;21(1):29–37.

Jenie RI, Handayani S, Susidarti RA, Udin Z, Meiyanto E. Cytotoxic and antimetastasis effect of ethyl acetate fraction from Caesalpinia sappan L. on MCF-7/HER2 cells. Indonesian Journal of Cancer Chemoprevention. 2017 Feb;8(1):42-50.

Yob NJ, Jofrry SM, Affandi MMRMM, Teh LK, Salleh MZ, Zakaria ZA. Zingiber zerumbet (L.) Smith: A review of its ethnomedicinal, chemical, and pharmacological uses. Evid Based Complement Alternat Med. 2011 Mar:543216.

Koga AY, Beltrame FL, Pereira A V. Several aspects of Zingiber zerumbet: a review. Rev Bras Farmacogn. 2016 Mei;26(3):385–91.

Murakami A, Tanaka T, Lee J-Y, Surh Y-J, Kim HW, Kawabata K, et al. Zerumbone, a sesquiterpene in subtropical ginger, suppresses skin tumor initiation and promotion stages in ICR mice. Int J Cancer. 2004 Jul;110(4):481–90.

Nakamura Y, Yoshida C, Murakami A, Ohigashi H, Osawa T, Uchida K. Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes. FEBS Letters. 2004;572(1–3):245–50.

Tsuboi K, Matsuo Y, Shamoto T, Shibata T, Koide S, Morimoto M, et al. Zerumbone inhibits tumor angiogenesis via NF-κB in gastric cancer. Oncol Rep. 2014;31(1):57–64.

Riss TL, Moravec RA, Niles AL, Duellman S, Benink HA, Worzella TJ, et al. Cell viability assays [Internet]. Assay guidance manual. Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2013 [dikutip 19 Maret 2018]. Tersedia pada: http://www.ncbi.nlm.nih.gov/pubmed/23805433

Hemalatha K, Sunitha D, Satyanarayana D. Cytotoxic activity of ethanolic extracts of Caesalpinia sappan Linn and Anona squamosa Linn in A-549 cell line. Int J Pharm Ind Res. 2011;01(04):318–21.

Hung TM, Dang NH, Dat NT. Methanol extract from Vietnamese Caesalpinia sappan induces apoptosis in HeLa cells. Biol Res. 2014;47(1):1-5.

Nurzijah I, Putri DDP, Rivanti E, Meiyanto E. Secang (Caesalpiniasappan L.) heartwood ethanolic extract shows activity as doxorubicin co-chemotherapeutic agent by apoptotis induction on T47D breast cancer cells. Indonesian Journal of Cancer Chemoprevention. 2012;3(2):377–84.

Norfazlina MN, Zuraina MYF, Rajab NF, Nazip SM, Rumiza AR, Zaila CFS, et al. Cytotoxicity study of Nigella sativa and Zingiber zerumbet extracts, thymoquinone and zerumbone isolated on human myeloid leukemia (HL60) cell. In: The Open Conference Proceedings Journal. 2014; 99–107.

Handayani S, Susidarti RA, Jenie RI, Meiyanto E. Two active compounds from Caesalpinia sappan L. in combination with cisplatin synergistically induce apoptosis and cell cycle arrest on WiDr cells. Adv Pharm Bull. 2017;7(3):375–80.

Kim B, Kim S-H, Jeong S-J, Sohn EJ, Jung JH, Lee MH, et al. Brazilin induces apoptosis and G2/M arrest via inactivation of histone deacetylase in multiple myeloma U266 cells. J Agric Food Chem. 2012 Oct;60(39):9882–9.

Kelley MR, Logsdon D, Fishel ML. Targeting DNA repair pathways for cancer treatment: what’s new? Futur Oncol. 2014;10(7):1215–37.

Carrassa L. Cell cycle, checkpoints and cancer. Atlas Genet Cytogenet Oncol Haematol. 2014;18(1):67–75.

Crowley LC, Marfell BJ, Scott AP, Waterhouse NJ. Quantitation of apoptosis and necrosis by annexin V binding, propidium iodide uptake, and flow cytometry. Cold Spring Harb Protoc. 2016 Nov;(11):953–7.

Sithara T, Dhanya BP, Arun KB, Sini S, Dan M, Kokkuvayil Vasu R, et al. Zerumbone, a cyclic sesquiterpene from Zingiber zerumbet induces apoptosis, cell cycle arrest, and antimigratory effects in SW480 colorectal cancer cells. J Agric Food Chem. 2018 Jan;66(3):602–12.

Mohammad RM, Muqbil I, Lowe L, Yedjou C, Hsu H-Y, Lin L-T, et al. Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol. 2015 Dec;35:S78–103.

Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N. Apoptosis and molecular targeting therapy in cancer. Biomed Res Int. 2014:150845

How to Cite
Haryanti S, Sholikhah I, Widiyastuti Y. Efek Sinergis Kombinasi Ekstrak Etanolik Kayu Secang dan Rimpang Lempuyang pada Sel Kanker Payudara MCF-7. jki [Internet]. 16May2019 [cited 27Mar.2023];9(1):1-. Available from: https://ejournal2.litbang.kemkes.go.id/index.php/jki/article/view/324