A Cytotoxic Activity of Ethanol Extract of Yellow Root Stem (Arcangelisia flava (L.) Merr.) and Its Effect on Expression of Bcl-2 and Bcl-xL Genes in MCF-7 Cells
Abstract
Breast cancer was the main cause of death in women on the world, the percentage of breast cancer deaths in Indonesia reaching 9.6% with a prevalence of 201,143 cases of total cancer cases in 2020. The increasing incidence of breast cancer caused the use of breast cancer drugs to increase, especially natural ingredients that could be used as an alternative treatment for breast cancer with minimal side effects. Yellow root (Arcangelisia flava (L.) Merr.) contained berberine compounds which was known to have cytotoxic activity. he aim of this study was to determine the cytotoxic activity of the yellow root stem extract (Arcangelisia flava (L.) Merr.) and its effect on the expression of Bcl-2 and Bcl-xL in MCF-7 breast cancer cells. Extraction was obtained by maceration method with 70% ethanol as solvent. The method of testing cytotoxic activity using the MTT method assay at the concentration series (2800; 1400; 700; 350; 175; 87.5; 43.75) μg/ml then calculated the IC50 value using linear regression. The narrative review was conducted by collecting data from various online research journals using the keywords cytotoxicity of extracts of yellow root (Arcangelisia flava (L.) Merr.) AND the effect on the expression of Bcl-2 and Bcl-xL genes in MCF-7 cells. The results of the cytotoxic test showed that the extract had cytotoxic activity against MCF-7 breast cancer cells with an IC50 of 838.67 μg/ml so that the cytotoxic effect was moderate (100-1000 μg/ml) and the results of the study of the effect of protein expression on cancer cells showed that berberine contained in yellow root can reduce the expression of Bcl-2 and Bcl-xL through the mitochondrial intrinsic pathway in MCF-7 breast cancer cells so that it can induce apoptosis induction.
Keywords:
Arcangelisia flava (L.) Merr; cytotoxic; MCF-7; Bcl-2; Bcl-xL
References
Arianingrum, R. et al. (2016) ‘Pengaruh p-HIDROSI m-Metoksi Kalkon (pHmMK) terhadap Ekspresi Protein Bcl-2 dan Bax pada Sel Kanker Payudara MCF-7’, Jurnal Penelitian Saintek, 21(1), pp. 10–20.
Azis, T., Febrizky, S. and Mario, A. D. (2014) ‘Pengaruh Jenis Pelarut Terhadap Persen Yieldalkaloiddari Daun Salam India (Murraya koenigii)’, Teknik Kimia, 20(2), pp. 1–6.
BPOM RI (2012) Pedoman Teknologi Formulasi Sediaan Berbasis Ekstrak. Jakarta: Badan POM RI. Available at: http://library1.nida.ac.th/termpaper6/sd/2554/19755.pdf.
BPOM RI (2014) ‘Persyaratan Mutu Obat Tradisional’, Peraturan Kepala Badan Pengawas Obat dan Makanan Republik Indonesia Nomor 12 Tahun 2014.
BPOM RI (2019) ‘Peraturan BPOM Nomor 32 Tahun 2019 Persyaratan Keamanan dan Mutu Obat Tradisional’, Badan Pengawas Obat dan Makanan, pp. 1–37.
Chen, Y. and Zhang, H. (2018) ‘Berberine and Chemotherapeutic Drugs Synergistically Inhibits Cell Proliferation and Migration of Breast Cancer Cells’, International Journal of Clinical and Experimental Medicine, 11(12), pp. 13243–13250.
Comşa, Ş., Cîmpean, A. M. and Raica, M. (2015) ‘The story of MCF-7 Breast Cancer Cell Line: 40 Years of Experience in Research’, Anticancer Research, 35(6), pp. 3147–3154.
Emilan, T. et al. (2011) Konsep Herbal Indonesia Pemastian Mutu Produk Herbal, Tesis. Universitas Indonesia. Available at: http://www.farmako.uns.ac.id/perhipba/wp-content/uploads/2012/01/MU.2.pdf.
Endarini, L. H. (2016) Modul Bahan Ajar Cetak Farmasi Farmakognisi dan Fitokimia. Jakarta Selatan: Pusdik SDM Kesehatan Badan Pengembangan dan Pemberdayaan Sumber Daya Manusia Kesehatan Kementerian Kesehatan RI.
Frihani, A. A., Indrayati, A. and Leviana, F. (2019) ‘Potensi Ekstrak Etanol Batang Akar Kuning (Arcangelisia flava (L.) Merr.) sebagai Antikanker Hati terhadap Kultur Sel HepG2’. Fakultas Farmasi Universitas Setia Budi Surakarta, pp. 1–19.
Han, Y., Wang, J. and Xu, B. (2020) ‘Clinicopathological Characteristics and Prognosis of Breast Cancer with Special Histological types: A Surveillance, Epidemiology, and End Results Database Analysis’, The Breast, 54, pp. 114–120. doi: 10.1016/j.breast.2020.09.006.
Haryanti, S. and Widiyastuti, Y. (2017) ‘Aktivitas Sitotoksik pada Sel MCF-7 dari Tumbuhan Indonesia untuk Pengobatan Tradisional Kanker Payudara’, Media Penelitian dan Pengembangan Kesehatan, 27(4), pp. 247–254. doi: 10.22435/mpk.v27i4.5010.247-254.
Hasan, H. and Moo, D. (2014) Senyawa Kimia dan Uji Efektivitas Ekstrak Tanaman Kayu Kuning (Arcangelisia flava L) dalam Upaya Pengembangan sebagai Bahan Obat Herbal, Laporan Bidang Ilmu Kesehatan.
International Agency for Research on Cancer (IARC) (2020) Indonesia - Global Cancer Observatory, Globocan.
Ismaryani, A. et al. (2018) ‘Aktivitas Sitotoksik, Antiproliferasi dan Penginduksi Apoptosis Daun Salung (Psychotria viridiflora reinw. ex. blume) terhadap Sel Kanker Serviks Hela’, Jurnal Ilmu Kefarmasian Indonesia, 16(2), pp. 206–213.
Isparnaning, I. Y., Puspitasari, E. and Pangaribowo, D. A. (2015) ‘Uji Sitotoksisitas Ekstrak Etanol Daun Arcangelisia flava pada Sel Kanker Payudara MCF-7’, 7, pp. 1–5.
Jabbarzadeh Kaboli, P. et al. (2014) ‘Targets and Mechanisms of Berberine, a Natural Drug with Potential to Treat Cancer with Special Focus on Breast Cancer’, European Journal of Pharmacology, 740, pp. 584–595. doi: 10.1016/j.ejphar.2014.06.025.
Kemenkes RI (2017) Farmakope Herbal Indonesia Edisi 2. Jakarta: Kementerian Kesehatan Republik Indonenesia.
Kurniandari, N., Susantiningsih, T. and Berawi, K. N. (2015) ‘Efek Ekstrak Etanol Kulit Jeruk Nipis (Citrus aurantifolia) sebagai Senyawa Nefroprotektor terhadap Gambaran Histopatologis Ginjal yang Diinduksi Cisplatin’, Majority, 4, pp. 140–143.
Lee, J. J. et al. (2020) ‘Cytotoxic Activity of Christia vespertilionis Root and Leaf Extracts and Fractions against Breast Cancer Cell Lines’, Molecules, 25(11), p. 2610. doi: 10.3390/molecules25112610.
Legowo, A. M., Nurwantoro and Sutaryo (2007) Buku Ajar Analisis Pangan.
Ma, X. et al. (2013) ‘Modulation of Drug-Resistant Membrane and Apoptosis Proteins of Breast Cancer Stem Cells By Targeting Berberine Liposomes’, Biomaterials, 34(18), pp. 4452–4465. doi: 10.1016/j.biomaterials.2013.02.066.
Muflihah, F., Rusli, R. and Febrina, L. (2015) ‘Optimalisasi Ekstraksi dan Uji Metabolit Sekunder Tumbuhan Libo’, J. Trop. Pharm. Chem, 3(2), pp. 74–81.
Nirwana, A. P. (2015) Aktivitas Antiproliferasi Ekstrak Etanol Daun Benalu Kersen (Dendrophtoe pentandra L. Miq.) terhadap Kultur Sel Kanker Nasofaring (Raji Cell Line), Tesis Program Studi Biosain. Universitas Sebelas Maret.
Patil, J. B., Kim, J. and Jayaprakasha, G. K. (2010) ‘Berberine Induces Apoptosis in Breast Cancer Cells (MCF-7) through Mitochondrial-dependent Pathway’, European Journal of Pharmacology, 645(1–3), pp. 70–78. doi: 10.1016/j.ejphar.2010.07.037.
Pratama, M. R. F., Mulyani, E. and Suratno, S. (2019) ‘Molecular Docking Study of Akar Kuning (Arcangelisia flava) Secondary Metabolites as Src Inhibitor’, Indonesian Journal of Cancer Chemoprevention, 10(3), p. 122. doi: 10.14499/indonesianjcanchemoprev10iss3pp122-130.
Pusat Data dan Informasi Kemenkes RI (2015) ‘Kanker’, Infodatin, 3 March, pp. 1–6.
Puspitasari, E. et al. (2015) ‘Ethanolic Extract of Arcangelisia flava leaves is Cytotoxic and Selective Againts Breast and Colon Cancer Cell Lines’, in Colaboration Approach to Improve Research and Management of Chronic Disease, pp. 82–86.
Putra, G. M. D. et al. (2018) ‘Standarisasi dan Skrining Fitokimia Ekstrak Etanol 70% Daun Jeruk Limau (Citrus amblycarpa (Hassk.) Osche)’, Jurnal Kimia, 12(2), pp. 187–194. doi: 10.24843/jchem.2018.v12.i02.p15.
Rafi, M., Heriyanto, R. and Septaningsih, D. (2017) Kendali Mutu Tumbuhan Obat Menggunakan Kromatografi Lapis Tipis. 1st edn. Bogor: IPB Press.
Sari, G. N. F. and Handayani, S. R. (2020) ‘The Effect Cytotoxic and Apoptotic Propagation Chloroform Fraction of Ocimum sanctum L. Towards Hela Cells Line Culture’, Biomedika, 13(1), pp. 31–39. doi: 10.31001/biomedika.v13i1.774.
Setyowati, R., Sudarsono, S. and P, S. E. (2014) ‘The Effect of Water-Soluble Stem Extract “Kayu Kuning“ (Arcangelisia flava L.Merr) on The Growth Inhibition of Candida albicans ATCC 10231 and Trichophyton mentagrophytes In Vitro’, Biology, Medicine, & Natural Product Chemistry, 3(1), p. 15. doi: 10.14421/biomedich.2014.31.15-19.
Umayah, E. and Rachmawati, E. (2016) ‘Standarisasi Ekstrak Batang Kayu Kuning (Arcangelisia flava ( L .) Merr)’, in Prosiding Seminar Nasional Tantangan Terkini Perkembangan Obat dan Aplikasi Klinis, pp. 20–25.
Utami, Y. P. et al. (2017) ‘Standardisasi Simplisia dan Ekstrak Etanol Daun Leilem (Clerodendrum minahassae Teisjm. & Binn.)’, Journal of Pharmaceutical and Medicinal Sciences, 2(1), pp. 32–39.
Utami, Y., Puspitasari, E. and Pangaribowo, D. A. (2015) ‘Uji Sitotoksisitas Ekstrak Etanol Terpurifikasi Daun Arcangelisia flava pada Sel Kanker Payudara MCF-7 (Cytotoxicity Assay of Purified Ethanol Extract of Arcangelisia flava Leaves on Breast Cancer Cells Mcf-7 )’, Artikel Ilmiah Hasil Penelitian Mahasiswa.
Widyanto, R. M. et al. (2020) ‘Aktivitas Antioksidan dan Sitotoksiksitas In Vitro Ekstrak Metanol Buah Nanas (Ananas comosus) pada Sel Kanker Payudara T-47D’, Jurnal Pangan dan Agroindustri, 8(2), pp. 95–103. doi: 10.21776/ub.jpa.2020.008.02.5.
Xie, J. et al. (2015) ‘Berberine-induced Apoptosis in Human Breast Cancer Cells is Mediated by Reactive Oxygen Species Generation and Mitochondrial-related Apoptotic Pathway’, Tumor Biology, 36(2), pp. 1279–1288. doi: 10.1007/s13277-014-2754-7.
Azis, T., Febrizky, S. and Mario, A. D. (2014) ‘Pengaruh Jenis Pelarut Terhadap Persen Yieldalkaloiddari Daun Salam India (Murraya koenigii)’, Teknik Kimia, 20(2), pp. 1–6.
BPOM RI (2012) Pedoman Teknologi Formulasi Sediaan Berbasis Ekstrak. Jakarta: Badan POM RI. Available at: http://library1.nida.ac.th/termpaper6/sd/2554/19755.pdf.
BPOM RI (2014) ‘Persyaratan Mutu Obat Tradisional’, Peraturan Kepala Badan Pengawas Obat dan Makanan Republik Indonesia Nomor 12 Tahun 2014.
BPOM RI (2019) ‘Peraturan BPOM Nomor 32 Tahun 2019 Persyaratan Keamanan dan Mutu Obat Tradisional’, Badan Pengawas Obat dan Makanan, pp. 1–37.
Chen, Y. and Zhang, H. (2018) ‘Berberine and Chemotherapeutic Drugs Synergistically Inhibits Cell Proliferation and Migration of Breast Cancer Cells’, International Journal of Clinical and Experimental Medicine, 11(12), pp. 13243–13250.
Comşa, Ş., Cîmpean, A. M. and Raica, M. (2015) ‘The story of MCF-7 Breast Cancer Cell Line: 40 Years of Experience in Research’, Anticancer Research, 35(6), pp. 3147–3154.
Emilan, T. et al. (2011) Konsep Herbal Indonesia Pemastian Mutu Produk Herbal, Tesis. Universitas Indonesia. Available at: http://www.farmako.uns.ac.id/perhipba/wp-content/uploads/2012/01/MU.2.pdf.
Endarini, L. H. (2016) Modul Bahan Ajar Cetak Farmasi Farmakognisi dan Fitokimia. Jakarta Selatan: Pusdik SDM Kesehatan Badan Pengembangan dan Pemberdayaan Sumber Daya Manusia Kesehatan Kementerian Kesehatan RI.
Frihani, A. A., Indrayati, A. and Leviana, F. (2019) ‘Potensi Ekstrak Etanol Batang Akar Kuning (Arcangelisia flava (L.) Merr.) sebagai Antikanker Hati terhadap Kultur Sel HepG2’. Fakultas Farmasi Universitas Setia Budi Surakarta, pp. 1–19.
Han, Y., Wang, J. and Xu, B. (2020) ‘Clinicopathological Characteristics and Prognosis of Breast Cancer with Special Histological types: A Surveillance, Epidemiology, and End Results Database Analysis’, The Breast, 54, pp. 114–120. doi: 10.1016/j.breast.2020.09.006.
Haryanti, S. and Widiyastuti, Y. (2017) ‘Aktivitas Sitotoksik pada Sel MCF-7 dari Tumbuhan Indonesia untuk Pengobatan Tradisional Kanker Payudara’, Media Penelitian dan Pengembangan Kesehatan, 27(4), pp. 247–254. doi: 10.22435/mpk.v27i4.5010.247-254.
Hasan, H. and Moo, D. (2014) Senyawa Kimia dan Uji Efektivitas Ekstrak Tanaman Kayu Kuning (Arcangelisia flava L) dalam Upaya Pengembangan sebagai Bahan Obat Herbal, Laporan Bidang Ilmu Kesehatan.
International Agency for Research on Cancer (IARC) (2020) Indonesia - Global Cancer Observatory, Globocan.
Ismaryani, A. et al. (2018) ‘Aktivitas Sitotoksik, Antiproliferasi dan Penginduksi Apoptosis Daun Salung (Psychotria viridiflora reinw. ex. blume) terhadap Sel Kanker Serviks Hela’, Jurnal Ilmu Kefarmasian Indonesia, 16(2), pp. 206–213.
Isparnaning, I. Y., Puspitasari, E. and Pangaribowo, D. A. (2015) ‘Uji Sitotoksisitas Ekstrak Etanol Daun Arcangelisia flava pada Sel Kanker Payudara MCF-7’, 7, pp. 1–5.
Jabbarzadeh Kaboli, P. et al. (2014) ‘Targets and Mechanisms of Berberine, a Natural Drug with Potential to Treat Cancer with Special Focus on Breast Cancer’, European Journal of Pharmacology, 740, pp. 584–595. doi: 10.1016/j.ejphar.2014.06.025.
Kemenkes RI (2017) Farmakope Herbal Indonesia Edisi 2. Jakarta: Kementerian Kesehatan Republik Indonenesia.
Kurniandari, N., Susantiningsih, T. and Berawi, K. N. (2015) ‘Efek Ekstrak Etanol Kulit Jeruk Nipis (Citrus aurantifolia) sebagai Senyawa Nefroprotektor terhadap Gambaran Histopatologis Ginjal yang Diinduksi Cisplatin’, Majority, 4, pp. 140–143.
Lee, J. J. et al. (2020) ‘Cytotoxic Activity of Christia vespertilionis Root and Leaf Extracts and Fractions against Breast Cancer Cell Lines’, Molecules, 25(11), p. 2610. doi: 10.3390/molecules25112610.
Legowo, A. M., Nurwantoro and Sutaryo (2007) Buku Ajar Analisis Pangan.
Ma, X. et al. (2013) ‘Modulation of Drug-Resistant Membrane and Apoptosis Proteins of Breast Cancer Stem Cells By Targeting Berberine Liposomes’, Biomaterials, 34(18), pp. 4452–4465. doi: 10.1016/j.biomaterials.2013.02.066.
Muflihah, F., Rusli, R. and Febrina, L. (2015) ‘Optimalisasi Ekstraksi dan Uji Metabolit Sekunder Tumbuhan Libo’, J. Trop. Pharm. Chem, 3(2), pp. 74–81.
Nirwana, A. P. (2015) Aktivitas Antiproliferasi Ekstrak Etanol Daun Benalu Kersen (Dendrophtoe pentandra L. Miq.) terhadap Kultur Sel Kanker Nasofaring (Raji Cell Line), Tesis Program Studi Biosain. Universitas Sebelas Maret.
Patil, J. B., Kim, J. and Jayaprakasha, G. K. (2010) ‘Berberine Induces Apoptosis in Breast Cancer Cells (MCF-7) through Mitochondrial-dependent Pathway’, European Journal of Pharmacology, 645(1–3), pp. 70–78. doi: 10.1016/j.ejphar.2010.07.037.
Pratama, M. R. F., Mulyani, E. and Suratno, S. (2019) ‘Molecular Docking Study of Akar Kuning (Arcangelisia flava) Secondary Metabolites as Src Inhibitor’, Indonesian Journal of Cancer Chemoprevention, 10(3), p. 122. doi: 10.14499/indonesianjcanchemoprev10iss3pp122-130.
Pusat Data dan Informasi Kemenkes RI (2015) ‘Kanker’, Infodatin, 3 March, pp. 1–6.
Puspitasari, E. et al. (2015) ‘Ethanolic Extract of Arcangelisia flava leaves is Cytotoxic and Selective Againts Breast and Colon Cancer Cell Lines’, in Colaboration Approach to Improve Research and Management of Chronic Disease, pp. 82–86.
Putra, G. M. D. et al. (2018) ‘Standarisasi dan Skrining Fitokimia Ekstrak Etanol 70% Daun Jeruk Limau (Citrus amblycarpa (Hassk.) Osche)’, Jurnal Kimia, 12(2), pp. 187–194. doi: 10.24843/jchem.2018.v12.i02.p15.
Rafi, M., Heriyanto, R. and Septaningsih, D. (2017) Kendali Mutu Tumbuhan Obat Menggunakan Kromatografi Lapis Tipis. 1st edn. Bogor: IPB Press.
Sari, G. N. F. and Handayani, S. R. (2020) ‘The Effect Cytotoxic and Apoptotic Propagation Chloroform Fraction of Ocimum sanctum L. Towards Hela Cells Line Culture’, Biomedika, 13(1), pp. 31–39. doi: 10.31001/biomedika.v13i1.774.
Setyowati, R., Sudarsono, S. and P, S. E. (2014) ‘The Effect of Water-Soluble Stem Extract “Kayu Kuning“ (Arcangelisia flava L.Merr) on The Growth Inhibition of Candida albicans ATCC 10231 and Trichophyton mentagrophytes In Vitro’, Biology, Medicine, & Natural Product Chemistry, 3(1), p. 15. doi: 10.14421/biomedich.2014.31.15-19.
Umayah, E. and Rachmawati, E. (2016) ‘Standarisasi Ekstrak Batang Kayu Kuning (Arcangelisia flava ( L .) Merr)’, in Prosiding Seminar Nasional Tantangan Terkini Perkembangan Obat dan Aplikasi Klinis, pp. 20–25.
Utami, Y. P. et al. (2017) ‘Standardisasi Simplisia dan Ekstrak Etanol Daun Leilem (Clerodendrum minahassae Teisjm. & Binn.)’, Journal of Pharmaceutical and Medicinal Sciences, 2(1), pp. 32–39.
Utami, Y., Puspitasari, E. and Pangaribowo, D. A. (2015) ‘Uji Sitotoksisitas Ekstrak Etanol Terpurifikasi Daun Arcangelisia flava pada Sel Kanker Payudara MCF-7 (Cytotoxicity Assay of Purified Ethanol Extract of Arcangelisia flava Leaves on Breast Cancer Cells Mcf-7 )’, Artikel Ilmiah Hasil Penelitian Mahasiswa.
Widyanto, R. M. et al. (2020) ‘Aktivitas Antioksidan dan Sitotoksiksitas In Vitro Ekstrak Metanol Buah Nanas (Ananas comosus) pada Sel Kanker Payudara T-47D’, Jurnal Pangan dan Agroindustri, 8(2), pp. 95–103. doi: 10.21776/ub.jpa.2020.008.02.5.
Xie, J. et al. (2015) ‘Berberine-induced Apoptosis in Human Breast Cancer Cells is Mediated by Reactive Oxygen Species Generation and Mitochondrial-related Apoptotic Pathway’, Tumor Biology, 36(2), pp. 1279–1288. doi: 10.1007/s13277-014-2754-7.
Published
2022-10-03
How to Cite
Safitri, D., Frihani, A., Nisa, S., Kresnadipayana, D., & Herdwiani, W. (2022). A Cytotoxic Activity of Ethanol Extract of Yellow Root Stem (Arcangelisia flava (L.) Merr.) and Its Effect on Expression of Bcl-2 and Bcl-xL Genes in MCF-7 Cells. Biomedika, 15(2), 55-70. https://doi.org/https://doi.org/10.31001/biomedika.v15i2.1309
Section
Articles
