Synergistic Effects of Doxorubicin and Cardenolid Glycosides of Calotropis Gigantea Root on Cervical Cancer Hela Cell Line

Roihatul Mutiah(1*), Risma Aprinda Kristanti(2), Siti Maimunah(3)

(1) Department of Biological Pharmacy, Faculty of Medicine and Health Science, Universitas Islam Negeri Maulana Malik Ibrahim, Malang
(2) Program Studi Pendidikan Dokter, Faculty of Medicine and Health Science, Universitas Islam Negeri Maulana Malik Ibrahim, Malang
(3) Department of Biological Pharmacy, Faculty of Medicine and Health Science, Universitas Islam Negeri Maulana Malik Ibrahim, Malang
(*) Corresponding Author


Cardenolid glycosides (CGs) has been known has high anticancer activity against several types of cancers, for example, breast cancer, lung cancer, prostate cancer, melanoma, neuroblastoma, myeloma and leukemia in the in vitro and in vivo research. The aim of our study was to know the synergistic potency of CGs improving the efficacy of doxorubicin in cervical cancer. Activities from combination of doxorubicin and CGs was measured by MTT colorimetric methode. Combination Index was used as combination efficacy parameter. The results showed that the IC50 of CGs was 1,023 μg/mL. CGs demonstrated selective activity in inhibiting the growth of HeLa cells by selectivity index > 3 (241.9). Combination test for CGs and Doxorubicin showed strong synergistic effect in doses 200 ug/mL Doxorubicin and 1.79 ug/mL CGs. The synergistic effect has been shown by 10 combination doses for the doses below the IC50. CGs increases the efficacy of Doxorubicin for the doses below the IC50, thus CGs can be recommended as co chemotherapy in cervical cancer treatment.


Ko-kemoterapi; Glikosida cardenolid; Co-chemotherapy; Cardenolid glycosides (CGs); Calotropis gigantea; HeLa Cells Line

Full Text:



American Cancer Society (2015) ‘Global Cancer Facts & Figures 3rd Edition.’, American Cancer Society, (800), pp. 1–64.

Habib, M. R., Aziz, M. A. and Karim, M. R. (2010) ‘Inhibition of Ehrlich’s ascites carcinoma by ethyl acetate extract from the flower of Calotropis gigantea L. in mice’, Journal of Applied Biomedicine, 8(1), pp. 47–54.

Habib, M. R. and Karim, M. R. (2011) ‘Evaluation of antitumour activity of Calotropis gigantea L. root bark against Ehrlich ascites carcinoma in Swiss albino mice.’, Asian Pacific journal of tropical medicine. Hainan Medical College, 4(10), pp. 786–90.

Mutiah R. (2014). Pengembangan Fitofarmaka antikanker “Panduan Teknik Pengembangan Obat Herbal Indonesia Menjadi Fitofarmaka. Uin Maliki Press.ISBN: 978-602-1190-26-5.pp 50-70

Muti, R., Griana, T. P., Ula, Q. N. and Andhyarto, Y. (2016) ‘The Effect of Calotropis gigantea Leaves Extract on Fibrosarcoma Growth and Caspase 3 Expression .’ International Journal Pharmaceutical and Clinical Research. 8(3), pp. 167–171.

Muti, R., Sukardiman, Widyawaruyanti, A. and Zulaikah, S. (2016) ‘Comparison of Ethanol Extract from Roots , Leaves , and Flowers of Calotropis gigantea. Alchemy, 18, pp. 1–4.

Mutiah, R., Sukardiman, Widyawaruyanti A, (2017) ‘Cytotoxic Effect Of Crude Extract And Fraction From Calotropis Gigantea Leaves On Human Colon Cancer Widr Cell Lines., International Journal Pharmacy and Pharmacetical Sciences. 9 (1), pp. 83-86 .

Mutiah R. (2017). Aktivitas Dan Mekanisme Bahan Aktif Antikanker Dari Fraksi Etil Asetat Akar Calotrophis Gigantea (L.) W.T Aiton Secara In Vitro Terhadap Sel Kanker Kolon Widr. Disertasi .Fakultas Farmasi Universitas Airlangga.

Seeka, C. and Sutthivaiyakit, S. (2010). Cytotoxic cardenolides from the leaves of Calotropis gigantea.’, Chemical & pharmaceutical bulletin, 58(5), pp. 725–728.

Tacar O, Sriamornsak P, and Dass CR. (2013). Doxorubicin: An Update on Anticancer Molecular Action, Toxicity and Novel Drug Delivery Systems. Journal of Pharmacy and Pharmacology. 65(2), pp. 157-170.

Wang, Z.-N., Wang, M.-Y., Mei, W.-L., Han, Z. and Dai, H.-F. (2008) ‘A new cytotoxic pregnanone from Calotropis gigantea.’, Molecules (Basel, Switzerland), 13(12), pp. 3033–3039.

Wong, S. K., Lim, Y. Y., Abdullah, N. R. and Nordin, F. J. (2011) ‘Assessment of antiproliferative and antiplasmodial activities of five selected Apocynaceae species.’, BMC complementary and alternative medicine. BioMed Central Ltd, 11(1), p. 3.

You, H., Lei, M., Song, W., Chen, H., Meng, Y., Guo, D. and Liu, X. (2013) ‘Cytotoxic cardenolides from the root bark of Calotropis gigantea’, Steroids. Elsevier Inc., 78(10), pp. 1029–1034.


Article Metrics

Abstract views : 3147 | views : 4086


  • There are currently no refbacks.

Copyright (c) 2017 Majalah Obat Tradisional

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

©Majalah Obat Tradisional (Traditional Medicine Journal)
 ISSN 2406-9086
Faculty of Pharmacy
Universitas Gadjah Mada