Antagonic Effect of Soursop Leaf Aqueous Extract and Doxorubicin Combination in MCF7 and T47D Breast Cancer Cell

Miranti Kania Dewi, Siti Annisa Devi Trusda, Lelly Yuniarti

Abstract


The success of breast cancer therapy is still not optimal and the side effects caused by breast cancer therapy. The use of standard drug combinations with herbs is often used as co-chemotherapy and is believed to increase the drug's effectiveness. However, research on the antagonistic effect of the drug combination is still minimal. This study examines the anticancer effect of soursop leaf aquoxes extract and the combined impact of doxorubicin on MCF7 and T47D breast cancer cells. This research is pure in vitro experimental study of MCF7 and T47D breast cancer culture cells at the Parasitology Laboratory of the Faculty of Medicine, Universitas Gadjah Mada in August 2018. Toxicity tests were carried out using the method of tetrazolium 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) to calculate cell viability. The IC50 value was obtained by analyzing probit regression calculation using SPSS software. The synergism of this compound with doxorubicin was determined based on the value of the Combination Index (CI) using a combination test with series 1/2 IC50, 3/8 IC50, 1/4 IC50, and 1/8 IC50 and the data was analyzed using Compusyn 1.0 software. In this study, the effect of soursop leaf preparations will be tested on T47D and MCF7 breast cancer cell cultures and assess the impacts of co-chemotherapy of soursop leaf aqueous extract with doxorubicin. This study showed that IC50 soursop leaf aqueous extract in T47D breast cancer culture was 84 μg/mL and in MCF7 166.5 μg/mL. In contrast, the combined test showed that soursop leaf aqueous extract was antagonistic with doxorubicin in both T47D and MCF7 cancer cell cultures.

 

EFEK ANTAGONIS KOMBINASI EXTRAK AIR DAUN SIRSAK DAN DOKSORUBISIN PADA KULTUR SEL KANKER MCF7 AND T47D

Keberhasilan terapi kanker payudara saat ini masih belum optimal dan terdapat efek samping yang ditimbulkan dari terapi kanker payudara tersebut. Penggunaan kombinasi obat standar dengan herbal sering digunakan sebagai ko-kemoterapi dan diyakini dapat meningkatkan efektivitas obat, tetapi penelitian mengenai efek antagonis kombinasi obat masih sangat terbatas. Penelitian ini mengkaji efek antikanker ekstrak air daun sirsak dan kombinasinya dengan doksorubisin pada sel kanker payudara MCF7 dan T47D. Penelitian ini merupakan eksperimental murni secara in vitro pada sel kanker payudara MCF7 dan T47D di Laboratorium Parasitologi Fakultas Kedokteran Universitas Gadjah Mada periode Agustus 2018. Uji toksisitas dilakukan menggunakan metode tetrazolium 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) untuk menghitung viabilitas sel. Nilai IC50 didapatkan melalui analisis menggunakan perhitungan regresi probit menggunakan perangkat lunak SPSS. Efek sinergis senyawa ini dengan doksorubisin ditentukan berdasar atas nilai Indeks Kombinasi (IK) menggunakan uji kombinasi dengan seri 1/2 IC50, 3/8 IC50, 1/4 IC50, dan 1/8 IC50 serta data dianalisis menggunakan perangkat lunak Compusyn 1.0. Efek sediaan daun sirsak pada penelitian ini akan diujikan terhadap kultur sel kanker payudara T47D dan MCF7 serta menilai efek ko-kemoterapi ekstrak air daun sirsak dengan doksorubisin. Hasil penelitian ini menunjukkan bahwa IC50 ekstrak air daun sirsak pada kultur sel kanker T47D adalah 84 μg/mL dan pada kultur sel kanker MCF7 166.5 μg/mL, sedangkan uji kombinasi memperlihatkan bahwa ekstrak air daun sirsak berefek antagonis dengan doksorubisin pada kultur sel kanker T47D dan MCF7.


Keywords


Antagonic effect; breast cancer; daun sirsak; doksorubisin; doxorubicin; efek antagonis; kanker payudara; MCF7; soursop leaf; T47D

Full Text:

PDF

References


DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, et al. Breast cancer statistics, 2019. CA Cancer J Clin. 2019;69(6):438–51.

Tao Z, Shi A, Lu C, Song T, Zhang Z, Zhao J. Breast cancer: epidemiology and etiology. Cell Biochem Biophys. 2015;72(2):333–8.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 2016;66(4):271–89.

Liana Y. Analisis faktor-faktor yang mempengaruhi keluarga dalam penggunaan obat tradisional sebagai swamedikasi di Desa Tuguharum Kecamatan Madang Raya. JKK. 2017;4(3):121–8.

Ismail. Faktor yang mempengaruhi keputusan masyarakat memilih obat tradisional di Gampong Lam Ujong. Idea Nurs J. 2015;6(1):7–14.

Rajesh V, Baby Kala M. Antiproliferative and chemopreventive effect of Annona muricata Linn. on Ehrlich ascites carcinoma and benzo[a]pyrene induced lung carcinoma. Orient Pharm Exp Med. 2015;15(4):239–56.

Zhou Y, Zhang AH, Sun H, Yan GL, Wang XJ. Plant-derived natural products as leads to antitumor drugs. Plant Sci Today. 2014;1(2):46–61.

Mitsiades CS, Davies FE, Laubach JP, Joshua D, San Miguel J, Anderson KC, et al. Future directions of next-generation novel therapies, combination approaches, and the development of personalized medicine in myeloma. J Clin Oncol. 2011;29(14):1916–23.

Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58(3):621–81.

Ashton JC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2015;75(11):2400.

Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70(2):440–6.

Ramos-Esquivel A, Víquez-Jaikel Á, Fernández C. Potential drug-drug and herb-drug interactions in patients with cancer: a prospective study of medication surveillance. J Oncol Pract. 2017;13(7):e613–22.

Scripture CD, Figg WD. Drug interactions in cancer therapy. Nat Rev Cancer. 2006;6(7):546–58.

Baharum Z, Akim A, Taufiq-Yap Y, Hamid R, Kasran R. In vitro antioxidant and antiproliferative activities of methanolic plant part extracts of Theobroma cacao. Molecules. 2014;19(11):18317–31.

Riss TL, Moravec RA, Niles AL, Duellman S, Benink HA, Worzella TJ, et al. Cell viability assays. In: Markossian S, Grossman A, Brimacombe K, Arkin M, Auld D, Austin CP, editors. Assay guidance manual [e-book]. Bethesda: Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2004 [updated 2016 July 1; cited 2020 July 10]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK144065.

van Meerloo J, Kaspers GJ, Cloos J. Cell sensitivity assays: the MTT assay. Methods Mol Biol. 2011;731:237-45.

Caamal-Fuentes EE, Peraza-Sánchez SR, Torres-Tapia LW, Moo-Puc RE. Isolation and identification of cytotoxic compounds from Aeschynomene fascicularis, a Mayan medicinal plant. Molecules. 2015;20(8):13563–74.

Rady I, Bloch MB, Chamcheu RCN, Banang Mbeumi S, Anwar MR, Mohamed H, et al. Anticancer properties of graviola (Annona muricata): a comprehensive mechanistic review. Oxid Med Cell Longev. 2018;2018:1826170.

Liu N, Yang HL, Wang P, Lu YC, Yang YJ, Wang L, et al. Functional proteomic analysis revels that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway. J Ethnopharmacol. 2016;189:210–7.

Salsabila IA, Nugraheni N, Ahlina FN, Haryanti S, Meiyanto E. Synergistic cotreatment potential of soursop (Annona muricata L.) leaves extract with doxorubicin on 4T1 cells with antisenescence and anti-reactive-oxygen-species. Iran J Pharm Res. 2021;20(2):57–67.

van Leeuwen RWF, Jansman FGA, van den Bemt PMLA, de Man F, Piran F, Vincenten I, et al. Drug–drug interactions in patients treated for cancer: a prospective study on clinical interventions. Ann Oncol. 2015;26(5):992–7.

van Leeuwen RW, Brundel DH, Neef C, van Gelder T, Mathijssen RH, Burger DM, et al. Prevalence of potential drug–drug interactions in cancer patients treated with oral anticancer drugs. Br J Cancer. 2013;108(5):1071–8.




DOI: https://doi.org/10.29313/gmhc.v9i3.8525

pISSN 2301-9123 | eISSN 2460-5441


Visitor since 19 October 2016: 

View My Stats


Free counters!


Global Medical and Health Communication is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.