Efek Sinergis Kombinasi Ekstrak Air Akar Batu (Gerrardanthus Macrorhizus) dengan Doxorubicin pada Sel Kanker Payudara T47D

  • Sari Haryanti Balai Besar Penelitian dan Pengembangan Tanaman Obat dan Obat Tradisional
Keywords: sitotoksik, cytotoxic

Abstract

Doxorubicin is one of the most widely used chemotherapy agents in cancer therapy. The clinical results of doxorubicin are limited by cardiotoxic side effects which correlates with dose. Combination of doxorubicin with natural agents is a promising strategy for reducing its therapeutic doses as well as decreasing cardiotoxic effects. This study was conducted to investigate cytotoxic activity of caudex Gerrardanthus macrorhizus aqueous extract and its combination with doxorubicin on T47D cells. Dried caudex powder was extracted by infusion method, evaporated in oven 400C to get dried extract (GM). The MTT assay was performed to determine cytotoxic effect, either alone or in combination. Flow cytometry is used to observe cell cycle profile and apoptotic induction. GM alone did not exhibit cytotoxic effects but caused morphological alteration in T47D cells. Nevertheless, GM 40 μg/mL was able to improve cytotoxic effect of doxorubicin to 51%. Combination of doxorubicin 3 nM and 40 μg/mL GMA inhibited cell cycle in G2/M phase. This combination also resulted apoptotic induction, compared to untreated cell and each single treatment. Based on the results, caudex G. macrorhizus is potential to be further investigated as a co-chemotherapy agent with doxorubicin.

Abstrak

Doxorubicin adalah salah satu agen kemoterapi yang digunakan secara luas dalam terapi kanker. Hasil klinis doxorubicin dibatasi oleh kardiotoksisitas yang berkorelasi dengan besaran dosis. Kombinasi doxorubicin dengan bahan alam merupakan strategi yang menjanjikan untuk mengurangi dosis terapetik doxorubicin sehingga dapat menurunkan efek samping kardiotoksik. Penelitian ini dilakukan untuk mengkaji aktivitas sitotoksik ekstrak air  caudex Gerrardanthus macrorhizus dan kombinasinya dengan doxorubicin pada sel T47D. Serbuk caudex G. macrorhizus (GM) kering diekstraksi dengan metode infusa, kemudian diuapkan dalam oven 400C. Uji MTT dilakukan untuk menguji efek sitotoksik ekstrak, baik tunggal maupun kombinasi dengan doxorubicin. Flow cytometry digunakan untuk mengetahui profil siklus sel dan induksi apoptosis. Hasil penelitian menunjukkan ekstrak tunggal tidak memberikan efek sitotoksik namun mengakibatkan perubahan morfologi pada sel T47D. Ekstrak GM 40 μg/mL mampu meningkatkan efek sitotoksik doxorubicin 3 nM hingga 51%. Kombinasi doxorubicin 3 nM dan ekstrak 40 μg/mL menghambat siklus sel pada fase G2/M dan meningkatkan induksi apoptosis, dibandingkan kontrol sel dan masing-masing perlakuan tunggalnya. Berdasarkan hasil penelitian ini, caudex G. macrorhizus berpotensi untuk diteliti lebih lanjut sebagai agen ko-kemoterapi dengan doxorubicin.

 

References

Youlden DR, Cramb SM, Yip CH, Baade PD. Incidence and mortality of female breast cancer in the Asia-Pacific region. Cancer Biol Med. Juni 2014;11(2):101–15.

Kementerian Kesehatan. Laporan Tim Riset Penyakit Tidak Menular: Tumor Payudara dan Lesi Prakanker Serviks. Badan Litbang Kesehatan, Jakarta: 2016.

Greenwald P. Science, medicine, and the future: Cancer chemoprevention. BMJ. 23 2002;324(7339):714–8.

Vejpongsa P, Yeh ETH. Prevention of Anthracycline- Induced Cardiotoxicity: Challenges and Opportunities. J Am Coll Cardiol. 2014;64(9):938– 45.

Tsao AS, Kim ES, Hong WK. Chemoprevention of cancer. CA Cancer J Clin. 2004;54(3):150–80.

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

Naithani R, Huma LC, Moriarty RM, McCormick DL, Mehta RG. Comprehensive review of cancer chemopreventive agents evaluated in experimental carcinogenesis models and clinical trials. Curr Med Chem. 2008;15(11):1044–71.

Smith G. Guide to Succulents of Southern Africa. Penguin Random House South Africa; 2011.p344.

Van Jaarsveld E. Indigenous House Plants. Veld & Flora. 1999;34–6.

Haryanti S dan Widiyastuti Y. Aktivitas Sitotoksik pada Sel MCF-7 dari Tumbuhan Indonesia untuk Pengobatan Tradisional Kanker Payudara. Media Penelitan dan Pengembangan Kesehatan;2017;27(4):247-254.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 16 Desember 1983;65(1–2):55–63.

Abcam. Cell cycle analysis with flow cytometry & propidium iodide [Internet]. Abcam, USA; 2012 [dikutip 16 Oktober 2018]. Tersedia pada: https:// www.abcam.com/protocols/flow-cytometricanalysis- of-cell-cycle-with-propidium-iodidedna- staining

Van Engeland M, Ramaekers FC, Schutte B, Reutelingsperger CP. A novel assay to measure loss of plasma membrane asymmetry during apoptosis of adherent cells in culture. Cytometry. 1 Juni 1996;24(2):131–9.

Patrick Reynolds C, Maurer BJ. Evaluating response to antineoplastic drug combinations in tissue culture models. Chemosensitivity Vol 1 Vitro Assays. 2005;173–183.

Riss TL, Moravec RA, Niles AL, Duellman S, Benink HA, Worzella TJ, dkk. Cell Viability Assays. Dalam: Sittampalam GS, Coussens NP, Brimacombe K, Grossman A, Arkin M, Auld D, dkk., editor. Assay Guidance Manual [Internet]. Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences; 2013 [dikutip 23 Februari 2018]. Tersedia pada: http://www.ncbi.nlm.nih.gov/ books/NBK144065/

Jiang L, Tixeira R, Caruso S, Atkin-Smith GK, Baxter AA, Paone S, dkk. Monitoring the progression of cell death and the disassembly of dying cells by flow cytometry. Nat Protoc. 2016;11(4):655–63.

Nambiar KS, Hegde V. Apoptosis detection modalities: A brief review. Int Dent Med J Adv Res. 2016;2(1):1–5.

Pietkiewicz S, Schmidt JH, Lavrik IN. Quantification of apoptosis and necroptosis at the single cell level by a combination of Imaging Flow Cytometry with classical Annexin V/ propidium iodide staining. J Immunol Methods. 2015;423:99–103.

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(11):953–7.

Fogarty CE, Bergmann A. Killers creating new life: caspases drive apoptosis-induced proliferation in tissue repair and disease. Cell Death Differ. 2017;24(8):1390–400.

Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res. 2011;30(1):1- 14.

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

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

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

Volkova M, Russell R. Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment. Curr Cardiol Rev.2011;7(4):214–20

Octavia Y, Tocchetti CG, Gabrielson KL, Janssens S, Crijns HJ, Moens AL. Doxorubicin-induced cardiomyopathy: From molecular mechanisms to therapeutic strategies. J Mol Cell Cardiol. 2012;52(6):1213–25

De Angelis A, Urbanek K, Cappetta D, Piegari E, Ciuffreda LP, Rivellino A, dkk. Doxorubicin cardiotoxicity and target cells: a broader perspective. Cardio-Oncol. 2016;2:2.

Zhao L, Zhang B. Doxorubicin induces cardiotoxicity through upregulation of death receptors mediated apoptosis in cardiomyocytes. Sci Rep. 2017;7:44735.

Published
2018-12-06
How to Cite
1.
Haryanti S. Efek Sinergis Kombinasi Ekstrak Air Akar Batu (Gerrardanthus Macrorhizus) dengan Doxorubicin pada Sel Kanker Payudara T47D. bpk [Internet]. 6Dec.2018 [cited 25Apr.2024];46(3):183-90. Available from: http://ejournal2.litbang.kemkes.go.id/index.php/bpk/article/view/878
Section
Articles