FRAKSI ETIL ASETAT KULIT BATANG FALOAK (Sterculia quadrifida R.Br ) MENGINDUKSI APOPTOSIS DAN SIKLUS SEL PADA SEL KANKER PAYUDARA T47D

Rollando Rollando, Kestrilia Rega Prilianti

Abstract


Faloak (Sterculia quadrifida R.Br) is one source of bioactive compounds that could be developed as chemotherapeutic agent. Empirically East Nusa Tenggara people use boiled water of faloak bark as a cure for hepatitis (types A, B, and C), and gastroenteritis. This study was performed to test anticancer activity fraction of n-hexane, ethyl acetate, ethanol, and methanol of ethanolic extract from faloak stem bark for the type of breast cancer cell line T47D, and normal cell types Vero using cytotoxic 3- (4,5-dimetilazol- 2-yl) -2,5-difeniltetrazolium bromide (MTT) test method. Ethanolic extract was subjected to column chromatography using different solvents polarity level as n-hexane, ethyl acetate, ethanol, and methanol. Testing the cytotoxic effects using the MTT assay in T47D breast cancer cells and normal Vero cells with EC50 parameter. Ethyl acetate fraction in inducing apoptosis and cell cycle modulation was observed with flowcytometry method. The test results cytotoxic fraction indicating the fraction of ethyl acetate has the lowest activity with EC50 of 24.88 μg/mL and selectivity index of 15.58. Ethyl acetate fraction effects an accumulation of cells in S phase (27.43%) in breast cancer cells T47D which is able to induce apoptosis. These results demonstrate that the ethyl acetate fraction can be developed as a chemotherapeutic agent in improving the effectiveness of breast cancer treatment.

Keywords


apoptotic; breast cancer; cell cycle; cytotoxicity; faloak

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References


Anonim, 2016. Bahaya Kanker Payudara Masih Mengintai. Diakses pada Juli 2016,http://health.kompas.com/read/2016/02/1/13313582/Bahaya.Kanker.Payudara.Masih.Mengintai.

Biswas, S.K., Huang, J., Persaud, S., dan Basu, A., 2004. Down-regulation of Bcl2 is Associated With Cisplatin Resistance in Human Small Cell Lung Cancer H69 Cells. Molecular Cancer Therapeutics, 3, 327–334.

Costanzo, V., Robertson, K., Ying, C.Y., Kim, E., Avvedoimento, E., Gottesman, M., et al., 2000. Reconstitution of an ATM-dependent Checkpoint that Inhibits Chromosomal DNA Replication following DNA Damage. Molecular Cell, 6, 649-659.

Crafword, K.W., and Bowen, W. D., 2002. Sigma-2 Receptor Agonists Activate A Novel Apoptotic Pathway and Potentiate Antineoplastic Drugs in Breast Tumor Cell Lines. Cancer Research, 62, 313-322.

Depkes, 1985. Tanaman Obat Indonesia, Jilid I. Departemen Kesehatan Republik Indonesia, Jakarta.

Dhar, S.N., Kolishetti, S., Lippard, dan Farokhzad, 2011. Re: Targeted Delivery of a Cisplatin Prodrug for Safer and More Effective Prostate Cancer Therapy In Vivo. Proceedings of the National Academy of Sciences, 1850–1855.

Di Leo, A., Tanner, M., Desmed, C., Paesman, M., Cardoso, F., Durbecq, V., et al., 2007. p-53 Gene Mutations as A Predictive Marker in A population of Advanced Breast Cancer Patients Randomly Treated with Doxorubicin or Docetaxel in The Context of A Phase III Clinical Trial. Annals of Oncology, 18, 997-1003.

Eastman, A., Kohn, E.A., Brown, M.K., Rathman, J., Livingstone, M., Blank, D.H., et al., 2002. A Novel Indolocarbazole, ICP-1, Abrogates DNA Damageinduced Cell Cycle Arrest and Enhances Cytotoxicity: Similarities and Differences to the Cell Cycle Checkpoint Abrogator UCN-01. Molecular Cancer Therapeutics, 1, 1067-1078.

Fabianus, R., 2012, Aktivitas Anticendawan Zat Ekstraktif Faloak (Sterculia comosa Wallich), Jurnal Kehutanan IPB, 67, 6-11.

Falck, J., Mailand, N., Syljuasen, R.G., Bartek, J., and Lukas J., 2001. The ATMChk2 Cdc25A Checkpoint Pathway Guards Against Radioresistant DNA Synthesis. Nature, 410, 842-847.

Florea, M.A. dan Busselberg, D., 2011. Cisplatin as an Anti-Tumor Drug: Celullar Mechanism of Activity, Drug Resistance and Induced Side Effect. Cancer, 3, 1351–1371.

Galm, U., Hager, M.H., Lanen, S.G.V., Ju, J., Thorson, J.S., and Shen, B., 2005. Antitumor Antibiotics: Bleomycin, Enediynes, and Mitomycin. Chemical Reviews, 105 (2), 739-758.

Goloudina, A., Yamaguchi, H., Chervyakova, D.B., Appella, E., Fornace A.J., and Bulavin, D.V., 2003. Regulation of Human Cdc25A Stability by Serine 75 Phosphorylation is Not Sufficient to Activate a S phase Checkpoint. Cell Cycle, 2 (5), 273.

Harborne, J.B., 1987. Metode Fitokimia: Penuntun Cara Modern Menganalisis Tumbuhan. ITB Bandung, Bandung.

IARC, 2012. Globocan 2012: Estimated Cancer Insidence, Mortality and Prevalence Worldwide in 2012. Diakses pada Juli 2016,http://globocan.iarc.fr/Pages/fact_sheets_population.aspx.

Jamieson, E.R. dan Lippard, S.J., 1999. Structure, Recognition, and Processing of Cisplatin - DNA Adducts. Chem Rev, 99, 2467–2498.

Kementrian Kesehatan Republik Indonesia, 2014. Profil Kesehatan Indonesia 2014, http://www.depkes.go.id/folder/view/01/structure-publikasi-data-pusat-data-dan-informasi.html.

Kim, K.H., Park, H.Y., Nam, J.H., Park, J.E., Kim, J.Y., Park, M.I., et al., 2005. The Inhibitory Effect of Curcumin on the Growth of Human Colon Cancer Cells (HT-29, WiDr) in Vitro. Korea J Gastroenterol, 4, 277–84.

Ma, C.X., Janetka, J.W., and Piwnica-Worms, H., 2010. Death by Releasing The Breaks: CHK1 Inhibitors as Cancer Therapeutics. Trends in Molecular Medicine, 17 (2), 88-96.

Mailand, N., Falck, J., Lukas, C., Syljuasen, R.G., Welcker, M., Bartek, J., et al., 2000. Rapid Destruction of Cdc25A in Response to DNA Damage. Science, 288, 1425-1429.

Masuda, T., Ohba, S., Kawada, M., Osono, M., Ikeda, D., Esumi, H., et al., 2006. Antitumor Effect of Kigamicin D on Mouse Tumor Models. The Journal ofAntibiotics, 59 (4), 209-214.

Milosavlievic, N., Duranton, C., Djerbi, N., Puech, P., Gounon, P., LagadicGossmann, D., et al., 2010. Nongenomic Effects Of Cisplatin: Acute Inhibition Of Mechanosensitive Transporters And Channels Without Actin Remodeling. Molecular and Cellular Pathobiology, 70, 7514–7522.

Mokhtar, J.M., Akbarzadeh, A., Hashemi, M., Javadi, G., Mahdian, R., Mehrabi, R.M., et al., 2012. Cisplatin Induces Downregulation of Bcl-2 in T47D Breast Cancer Cell line. Advanced Studies in Biology, 4, 19–25.

Prayong, P., Barusrux, S., and Weerapreeyakul, N., 2008. Cytotoxic Activity Screening of Some Indigenous Thai Plants. Fitoterapia, 79, 598-601.

Preobrazhenskaya, M.N., Tevyashova, A.N., Olsufyeva, E.N., Huang, K.F., and Huang, H.S., 2006. Second Generation Drugs-derivatives of Natural Antitumor Anthracycline Antibiotics Daunorubicin, Doxorubicin and Carminomycin. Journal of Medical Sciences, 26 (4), 119-128.

Rollando, 2016, Penelusuran Potensi Aktivitas Antibakteri dan Antioksidan Fraksi Kulit Pohon Faloak (Sterculia quadrifida R.Br). Jurnal Kefarmasian, 4, 1-5.

Ross, J.S., Linette, G.P., Stec, J., Ross, M.S., Anwar, S., dan Boguniewics, A., 2003. DNA Ploidy and Cell Cycle Analysis in Breast Cancer. Am J Clin Pathol, 120, 572–584.

Schafer, J.M., Lee, E.S., O'Regan, R.M., Yao, K., and Jordan, V.C., 2000. Rapid Development of Tamoxifen-Stimulated Mutant p53 Breast Tumors (T47D) inAthymic Mice. Clinical Cancer Research, 6, 4373-4380.

Siswadi, Rianawati, H., Saragih, G., dan Hadi, D., 2013. The Potency of Faloak's (Sterculia quadrifida R.Br ) Active Compunds As Natural Remedy, Prosiding Seminar International, Kementrian Kehutanan bagian Penelitian dan Pengembangan Hutan, Bogor.

Tacar, O., Sriamornsak, P., and Dass, C.R., 2012. Doxorubicin: An Update on Anticancer Molecular Action, Toxicity and Novel Drug Delivery Systems. Journal of Pharmacy and Pharmacology, 65, 157-170.

Vayssade, M., Haddada, H., Faridoni-Laurens, L., Tourpin, S., Valent, A., Benard J, et al., 2005. p73 Functionally Replaces p53 in Adriamycin-treated, p53-deficient Breast Cancer Cells. International Journal of Cancer, 116 (6), 860-869.

Wagner, H., and Bladt, S., 1996. Plant Drug Analysis: A Thin Layer Chromatography Atlas, 2nd Edition, Springer-Verlag Berlin Heidelberg, New York.

Wang, W., Rayburn, E.R., Velu, S.E., Chen, D., Nadkarni, D.H., Murugesan, S., et al., 2010. A Novel Synthetic Iminoquinone, BA-TPQ, as an Anti-Breast Cancer Agent: In Vitro and In Vivo Activity and Mechanisms of Action. Breast Cancer Research and Treatment, 123, 321-331.

WHO, 2016. Cancer. Diakses pada Juli 2016,http://www.who.int/mediacentre/factsheets/fs297/en/.

Wong, H.L., Bendayan, R., Rauth, A.M., Xue, H.Y., Babakhanian, K., and Wu, X.Y., 2006. A Mechanistis Study of Enhanced Doxorubicin Uptake and Retention in Multidrug Resistant Breast Cancer Cells Using a Polymer Lipid Hybrid Nanoparticle System. The Journal of Pharmacology and Experimental Therapeutics, 317 (3), 1327-1381.

Zabludoff, S.D., Deng, C., Grondine, M.R., Sheehy, A.M., Ashwell, S., Caleb, B.L., et al., 2008. AZD7762, A Novel Checkpoint Kinase Inhibitor, drives Checkpoint Abrogation and Potentiates DNA-targeted Therapies. Molecular Cancer Therapeutics, 7, 2955-2966.

Zhang, G., Gurtu, V., Kain, S.R., dan Yan, G., 1997. Early Detection of Apoptosis Using a Fluorescent Conjugate of Annexin V. BioTechnique, 23, 525–531.




DOI: http://dx.doi.org/10.24071/jpsc.141557

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