Main Article Content

Abstract

Background: HER2+ breast cancer is a very aggressive type of breast cancer. Although trastuzumab, specifically targeted for HER2, has been used for breast cancer treatments, some patients become resistant to trastuzumab. A marine sponge is one of the potential sources of anticancer agents. One of marine sponges commonly found in Indonesia is Stylissa carteri, but it has not been explored extensively.
Objective: This study aimed to identify cytotoxic effects of the ethyl acetate fraction of Stylissa carteri on HCC-1954, HER2+ trastuzumab-resistant breast cancer cells, by assessing cell viability and determining IC50 value.
Methods: This study was an experimental in vitro study conducted in The Cell Culture Laboratory, Faculty of Medicine Universitas Padjadjaran on February 2018 to June 2018. The Stylissa carteri was collected from Pramuka Island, Kepulauan Seribu National Park Jakarta. HCC-1954 cells were treated by serial concentration of fractions and were incubated for 72 hours. Cell viability were observed under a microscope and analysed with MTT assay. The IC50 value was also determined by using four parametric logistic regression (4PL) method by Sigmaplot version 12.0.
Result: Data of this study showed descent of cell viability significantly when exposing the ethyl acetate fraction of Stylissa carteri. There was a decrease of 49% cell viability in 10 µg/ml of the ethyl acetate fraction of Stylissa carteri. The estimated IC50 value was 9.25 µg/ml.
Conclusion: This result indicated that the ethyl acetate fraction of Stylissa carteri has cytotoxic effects on HER2+ trastuzumab-resistant breast cancer cells.

Keywords

breast cancer cell viability HER2 positive marine sponge trastuzumab resistance Stylissa carteri

Article Details

How to Cite
Jannah, J. N., Fianza, P. I., Putri, T., & Bashari, M. H. (2019). The ethyl acetate fraction of sponge Stylissa carteri decreases viability in HER2+ trastuzumab-resistant breast cancer cells. JKKI : Jurnal Kedokteran Dan Kesehatan Indonesia, 10(3), 239–245. https://doi.org/10.20885/JKKI.Vol10.Iss3.art6

References

  1. WHO. WHO _ Cancer [Internet]. WHO. World Health Organization; 2017. Available from: http://www.who.int/mediacentre/factsheets/fs297/en/
  2. Soediono B, Kementerian Kesehatan RI, Kementerian Kesehatan Republik Indonesia. Situasi Penyakit Kanker. 2015.
  3. CDC - Breast Cancer.
  4. Dai X, Li T, Bai Z, Yang Y, Liu X, Zhan J, et al. Breast cancer intrinsic subtype classification, clinical use and future trends. American Journal of Cancer Research. 2015;5(10):2929–43.
  5. Eroles P, Bosch A, Alejandro Pérez-Fidalgo J, Lluch A. Molecular biology in breast cancer: Intrinsic subtypes and signaling pathways. Cancer Treatment Reviews. 2012;38(6):698–707.
  6. Toss A, Cristofanilli M. Molecular characterization and targeted therapeutic approaches in breast cancer. Breast Cancer Research. 2015;17(1):60.
  7. Makki J. Diversity of breast carcinoma: Histological subtypes and clinical relevance. Clinical Medicine Insights: Pathology. 2015;8:23–31.
  8. Yersal O, Barutca S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World Journal of Clinical Oncology. 2014;5(3):412–24.
  9. Cho N. Molecular subtypes and imaging phenotypes of breast cancer. Ultrason (Seoul, Korea). 2016;35(4):281–8.
  10. Gutierrez C, Schiff R. HER2: Biology, detection, and clinical implications. Archives of Pathology & Laboratory Medicine. 2011;135:55–62.
  11. Pohlmann PR, Mayer IA, Mernaugh R. Resistance to trastuzumab in breast cancer. Clinical Cancer Research. 2009;15(24):7479–91.
  12. Kim SK, Li YX. Handbook of anticancer drugs from marine origin. Springer International Publishing. Switzerland. 2015; p: 1–805.
  13. Schumacher M, Kelkel M, Dicato M, Diederich M. Gold from the sea: Marine compounds as inhibitors of the hallmarks of cancer. Biotechnology Advances. 2011;29(5):531–47.
  14. Oh H, Jensen PR, Murphy BT, Fiorilla C, Sullivan JF, Ramsey T, et al. Cryptosphaerolide, a cytotoxic Mcl-1 inhibitor from a marine-derived ascomycete related to the genus Cryptosphaeria. Journal of Natural Products. 2010;73(5):998–1001.
  15. U.S. Food and Drug Administration. Drugs@FDA: FDA Approved Drug Products [Internet]. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&applno=201532
  16. Smith JA, Wilson L, Azarenko O, Zhu X, Lewis BM, Littlefield BA, et al. Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability. Biochemistry. 2010;49(6):1331–7.
  17. Jimeno A. Eribulin: Rediscovering tubulin as an anticancer target. Clinical Cancer Research. 2009;15(12):3903–5.
  18. Cortes J, Vahdat L, Blum JL, Twelves C, Campone M, Roché H, et al. Phase II study of the halichondrin B analog eribulin mesylate in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, a taxane, and capecitabine. Journal of Clinical Oncology. 2010;28(25):3922–8.
  19. Dewi AS. When east meets west: The chemistry of Indonesian sponges and Australian nudibranchs. The University of Queensland; 2017.
  20. J. Boohaker R, W. Lee M, Vishnubhotla P, M. Perez JL, R. Khaled A. The use of therapeutic peptides to target and to kill cancer cells. Current Medicinal Chemistry. 2012;19(22):3794–804.
  21. Hardani IN, Damara FA, Nugrahani AD, Bashari MH. Ethanol extract of Stylissa carteri induces cell death in parental and paclitaxel-resistant cervical cancer cells. International Journal of Integrated Health Sciences. 2018;6(2):91–6.
  22. Bashari MH, Huda F, Tartila TS, Shabrina S, Putri T, Qomarilla N, et al. Bioactive compounds in the ethanol extract of marine sponge Stylissa carteri demonstrates potential anti-cancer activity in breast cancer cells. Asian Pacific Journal of Cancer Prevention. 2019;20(4):1199–206.
  23. Prayong P, Barusrux S, Weerapreeyakul N. Cytotoxic activity screening of some indigenous Thai plants. Fitoterapia. 2008;79(7–8):598–601.
  24. Hassan SS ul, Shaikh AL. Marine actinobacteria as a drug treasure house. Biomed Pharmacotherapy. 2017;87(4):46–57.
  25. Rivai H, Meliyana, Handayani D. Karakterisasi ekstrak spon laut Axinella carteri dendy secara fisika, kimia dan fisikokimia. Jurnal Farmasi Higea. 2010;2(1):1–12.
  26. Patel K, Laville R, Martin MT, Tilvi S, Moriou C, Gallard JF, et al. Unprecedented stylissazoles A-C from Stylissa carteri: Another dimension for marine pyrrole-2-aminoimidazole metabolite diversity. Angewandte Chemie International Edition. 2010;49(28):4775–9.