Awar-Awar Leaves Ethanolic Extract Sinergistically Enhances Cytotoxic Effect of Doxorubicin on T47D Breast Cancer Cells



Awar awar leaves which have not been optimally utilized in cancer treatment, are potential to be used in combination with doxorubicin (DOX), an agent used for chemotherapy. The aim of this experiment is to find out cytotoxic effect of awar-awar leaves ethanolic extract (ALE) and its combination with DOX towards breast cancer cells of T47D. ALE was prepared by macerating the dried-leaves powder with ethanol 70%. The cytotoxic effect of ALE toward breast cancer cells was tested employing MTT assay to the treatments both as a single agent and as a combination with doxorubicin (ALE DOX). The cytotoxicity was determined as IC50 value, while effectiveness of combination was measured by combination index (CI) to determine whether the effect is synergic, addictive, or antagonistic. Cytotoxic tests on single treatment ALE for a period of 24 hours resulted to a cytotoxic effect with IC so value of 13 µg/mL. ALE-DOX combination showed synergistic effect (CI < 1) on the concentration of 4.88 µg/mL (ALE) and 3.75 nM (DOX). The results showed that ALE is potential to be used as doxorubicin co-chemotherapeutic agent in breast cancer therapy.


1. King, RIB. Cancer Biology. 2nd Ed. London: Pearson Education Limited; 2000.

2. Staerk D, Lykkeberg AK, Christensen J, Budnik BA, Abe F, and Jaroszewski W. In vitro cytotoxic activity of phenanthroindolizidine alkaloids from Cynanchum vincetoxicum and Tylophora tanakae against drugsensitive and multidrug resistant cancer cells. J Nat Prod. 2002. 65:1299-1302.

3. Gunawan SG. Farmakologi dan Terapi. Ed ke-5. Jakarta: Bagian Farmakologi Fakultas Kedokteran Universitas Indonesia; 2007.

4. Wattanapitayakul SK, Chularojmontri L, Herunsalee A, Charuchongkolwongse S, Niumsakul, S, and Bauer, JA. Screening of antioxidants from medicinal plants for cardioprotective effect against doxorubicin toxicity. Basic & Clinical Pharmacology & Toxicology. 2005; 96:80.

5. Nurcahya BM. Efek antiproliferatif ekstrak etanolik daun awar-awar (Ficus septica Burm.F.) terhadap sel kanker payudara T47D. Skripsi. Yogyakarta: Fakultas Farmasi Universitas Gadjah Mada; 2007.

6. Sekti DA. Aktivitas sitotoksik, induksi apoptosis, dan modulasi ekspresi protein Bel-2 ekstrak etanolik daun awar-awar (Ficus Septica Burm. F.) pada sel kanker payudara MCF7. Skripsi. Yogyakarta: Fakultas Farmasi Universitas Gadjah Mada; 2009.

7. Mubarok FM, Sekti DA, Wulandari A, Jenie RI, Septisetyani EP, and Meiyanto E. Peningkatan aktivitas sitotoksik doxorubicin terhadap sel kanker payudara MCF-7 menggunakan ekstrak etanolik daun awar-awar (Ficus septica Burm F.). Kongres Ilmiah XVI ISFI. 2008:53.

8. Sharma G, Tyagi AK, Singh RP, Chan DCF, and Agarwal R. Synergistic Anti-cancer effect of grape seed extract and conventional cytotoxic againts human breast carcinoma cells. Breast Cancer Research and Treatment. 2004. 8:51-62.

9. Reynolds CP and Maurer BJ. Evaluating response to antineoplastic drug combinations in tissue culture models. Methods Mol Med. 2005. 110:173-83.

10. Fitriasari A, Junedi S, Hermawan A, Susidarti RA, and Meiyanto E. Induction of apoptosis and cell cycle arrest by naringenin to increase the cytotoxic activity of doxorubicin on breast cancer cell lines. The International Conference on Pharmacy and Advance Pharmaceutical Science. 2009:124.

11. Tyagi AK, Agarwal C, Chan DCF, and Agarwal R. Synergistic anti cancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 Cells. Oncology Reports. 2004. 11:493-9.

12. Ikhtiarsyah YG, Ikawati I, Hardika R, Nur W N, Fitriasari A, and Jenie RI. Awar-awar (Ficus sptica Burm F.) leaves ethanolic extract increases immune system and gives synergistic effect in combination with doxorubicin on breast cancer therapy. International Conference on Pharmacy and Advance Pharmaceutical Science. 2009. 130.

13. Wu PL, Rao KV, Su CH, Kuoh CS, Wu TS. Phenanthroindolizidine alkaloids and their cytotoxicity from the leaves of Ficus septica. Heterocycles. 2002. 57(12):2401-8.

14. Rao KN and Venkatachalam SR. Inhibition of dihydrofolate reductase and cell growth activity by the phenanthroindolizidine alkaloids pergularinine and tylophorinidine: the in vitro cytotoxicity of these plant alkaloids and their potential as antimicrobial and anticancer agents. Toxicol In Vitro. 2000. 14:53-9.

15. Davis JM, Navolanic PM, Weinstein-Oppenheimer CR, Steelman LS, Wei H, Konopleva M, Blagosklonny MV, and McCubrey JA. Raf-1 and Bel-2 induce distinct and common pathways that contribute to breast cancer drug resistance. Clinical Cancer Research. 2003. 9: 1161-70.

16. Notarbartolo M, Poma P, Perri D, Dusonchet L, Cervello M, and Alessandro N. Antitumor effects of curcumin, alone or in combination with cisplatin or doxorubicin on human hepatic cancer cell analysis of their possible relationship to changes in NF-kB activation levels and in IAP gene expression. Cancer Letter. 2005. 224:53-65.

17. Kitagawa S. Inhibitory effect of polyphenols on p-glycoprotein-rnediated transport. Biol Pharm Bull. 2006, 29(1):1-6.
How to Cite
PRATAMA, RATIH HARDIKA et al. Awar-Awar Leaves Ethanolic Extract Sinergistically Enhances Cytotoxic Effect of Doxorubicin on T47D Breast Cancer Cells. JURNAL ILMU KEFARMASIAN INDONESIA, [S.l.], v. 9, n. 1, p. 67-71, apr. 2011. ISSN 2614-6495. Available at: <>. Date accessed: 19 oct. 2021.