Cytotoxicity and Antiproliferative Activities of Ethanolic Peel Extract of Pyrus malus L. on T47D Cells
Abstract
Quercetin, a flavonoid compound in green apple peel (Pyrus malus L.), has shown anticancer potential in T47D cells. This study evaluated the cytotoxic effects and antiproliferative activities demonstrated by the Ethanolic Extract of Green Apple Peel (EEGAP) on T47D cells. The peel powder was extracted using 70% ethanol with ultrasonic waves. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed for the cytotoxicity test using EEGAP concentrations of 31.25, 62.5, 125, 250, 500, and 1,000 µg/mL. The IC50 value was determined using probit analysis. Based on the IC50 results, an antiproliferative assay was conducted using the doubling time technique at concentrations of ½IC50 (404.5 µg/mL) and IC50 (809 µg/mL), which were observed at 0, 24, 48, and 72 hours. EEGAP has a moderate cytotoxic effect, with an IC50 value of 809 µg/mL. EEGAP showed significant antiproliferative activity, with a doubling time of 14 hours in control samples. EEGAP at a concentration of ½ IC50 showed a replication period of 21 hours, whereas the IC50 concentration replication period was 30 hours. These results suggest that EEGAP exhibits cytotoxic and antiproliferative properties, which may have potential as a natural compound for breast cancer therapy.
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References
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Martino E, Vuoso DC, D’Angelo S, Mele L, D’onofrio N, Porcelli M, et al. Annurca Apple Polyphenol Extract Selectively Kills MDA-MB-231 Cells through ROS Generation, Sustained JNK Activation and Cell Growth and Survival Inhibition. Scientific Reports. 2019;9(1):13045. Crossref
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Susilowati S, Anggraini TD. Efek Sitotoksisitas dan Selektivitas Fraksi Aktif Ekstrak Daun Kelor (Moringa oleifera Lamk.) terhadap Sel Kanker Payudara T47D. Farmasains: Jurnal Ilmiah Ilmu Kefarmasian. 2018;5(2):50–54. Crossref
Riwanti P, Izazih F, Amaliyah A. Pengaruh Perbedaan Konsentrasi Etanol pada Kadar Flavonoid Total Ekstrak Etanol 50, 70 dan 96% Sargassum polycystum dari Madura. Journal of Pharmaceutical Care Anwar Medika (J-PhAM). 2020;2(2):82–95. Crossref
Sair AT, Li Y, Zhao W, Li T, Liu RH. Anticancer Activity of Apple Peel Extracts Against Human Breast Cancer Cells through Insulin-Like Growth Factor-1 Signal Transduction Pathway. Journal of Agriculture and Food Research. 2023;11:100507. Crossref
Setiawan SI, Safitri EI, Muna LN, Hidayati DN. Aktivitas Sitotoksik dan Induksi Apoptosis dari Ekstrak Etanol Kulit Apel Hijau (Pyrus malus L.) terhadap Sel MCF-7. Jurnal Pharmascience. 2021;8(2):69-78. Crossref
Kalinowska M, Bielawska A, Lewandowska-Siwkiewicz H, Priebe W, Lewandowski W. Apples: Content of Phenolic Compounds vs. Variety, Part of Apple and Cultivation Model, Extraction of Phenolic Compounds, Biological Properties. Plant Physiology and Biochemistry. 2014;84:169-188. Crossref
Lin ST, Tu SH, Yang PS, Lee WH, Ho CT, Wu CH, et al. Apple Polyphenol Phloretin Inhibits Colorectal Cancer Cell Growth via Inhibition of The Type 2 Glucose Transporter and Activation of p53-Mediated Signaling. Journal of Agricultural and Food Chemistry. 2016;64(36):6826-6837. Crossref
Nezbedova L, McGhie T, Christensen M, Heyes J, Nasef NA, Mehta S. Onco-Preventive and Chemo-Protective Effects of Apple Bioactive Compounds. Nutrients. 2021;13(11):4025. Crossref
Eff ARY. In-vitro Cytotoxic Assay 50% Ethanol Extract Kitolod (Isotoma longiflora (L.) Presl.) Leaf Against Cervical Cancer Cells (Ca Ski Cell Line). Farmasains: Jurnal Ilmiah Ilmu Kefarmasian. 2016;3(1):7–12.
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 Journal for Clinicians. 2018;68(6):394–424. Crossref
Feng Y, Spezia M, Huang S, Yuan C, Zeng Z, Zhang L, et al. Breast Cancer Development and Progression: Risk Factors, Cancer Stem Cells, Signaling Pathways, Genomics, and Molecular Pathogenesis. Genes & Diseases. 2018;5(2):77–106. Crossref
Yu S, Kim T, Yoo KH, Kang K. The T47D Cell Line is an Ideal Experimental Model to Elucidate the Progesterone-Specific Effects of a Luminal A Subtype of Breast Cancer. Biochemical and Biophysical Research Communications. 2017;486(3):752–758. Crossref
Jennifer H, Saptutyningsih E. Preferensi Individu terhadap Pengobatan Tradisional di Indonesia. Jurnal Ekonomi & Studi Pembangunan. 2015;16(1):26–41.
Ardiansyah A, Budiya B, Cahyanto B. Pengolahan Limbah Kulit Apel menjadi Minuman Tradisional Menyehatkan Warga Desa Wringinanom Kabupaten Malang. E-Dimas: Jurnal Pengabdian kepada Masyarakat. 2024;15(1):99–105. Crossref
Srivastava S, Somasagara RR, Hegde M, Nishana M, Tadi SK, Srivastava M, et al. Quercetin, a Natural Flavonoid Interacts with DNA, Arrests Cell Cycle and Causes Tumor Regression by Activating Mitochondrial Pathway of Apoptosis. Scientific Reports. 2016;6(1):24049. Crossref
Naushafira ND, Hanuna H, Dewi MK, Selius WVN. Kajian Sistematik: Aktivitas Kuersetin sebagai Inhibitor Kanker Payudara secara In Vitro. Generics: Journal of Research in Pharmacy. 2022;2(2):105–112. Crossref
Authoria N, Wijayanti L, Febrinasari RP. Differences of Quercetin Content in Fresh and Extracts Local Apples using High Performance Liquid Chromatography Method. Journal Healthcare Biomedical Science. 2022;1(1):24–35. Crossref
Pertiwi RD, Yari CE, Putra NF. Uji Aktivitas Antioksidan Ekstrak Etanol Limbah Kulit Buah Apel (Malus domestica Borkh.) terhadap Radikal Bebas DPPH (2,2-Diphenyl-1-Picrylhydrazil). Jurnal Ilmiah Manuntung. 2016;2(1):81–92.
1Hartanti F, Hidayati DN. Antibacterial Activities of Papaya Seed (Carica papaya L.) Ethanol Extract with MAE And UAE Extraction Methods Towards Staphylococcus aureus. Jurnal Media Farmasi. 2023;20(2):51-56. Crossref
1Cancer Chemoprevention Research Center (CCRC). Uji Sitotoksik Metode Microculture Tetrazolium Test. Yogyakarta: Fakultas Farmasi UGM; 2009. p. 6–9.
Widyanto RM, Putri JA, Rahmi Y, Proborini WD, Utomo B. Aktivitas Antioksidan dan Sitotoksisitas In Vitro Ekstrak Metanol Buah Nanas (Ananas comosus) pada Sel Kanker Payudara T-47D. Jurnal Pangan dan Agroindustri. 2020;8(2):95–103. Crossref
Sukma LC, Da’i M. Uji Aktivitas Antiproliferatif dan Induksi Apoptosis Ekstrak Etanol Daun Kemangi (Ocimum sanctum L.) terhadap Sel MCF-7. Usadha: Journal of Pharmacy. 2022;1(2):177–185. Crossref
Fauziah L, Wakidah M. Extraction of Papaya Leaves (Carica papaya L.) using Ultrasonic Cleaner. EKSAKTA: Journal of Sciences and Data Analysis. 2019;19(1):35–45. Crossref
1Dona R, Sulistyani N, Nurani LH. Uji Sitotoksisitas dan Antiproliferatif Ekstrak Etanol Daun Leunca (Solanum nigrum L.) terhadap Sel Raji. Pharmaciana. 2016;6(2):181–190. https://doi.org/10.12928/pharmaciana.v6i2.3506">Crossref
Helilusiatiningsih N, Yunianta A, Harijono A, Wijanarko SB. Cytotoxic Activity and Selectivity Index of Solanum torvum Fruit on T47D Breast. Indian Journal of Public Health Research & Development. 2020;11(1):1364-1369. Crossref
Martino E, Vuoso DC, D’Angelo S, Mele L, D’onofrio N, Porcelli M, et al. Annurca Apple Polyphenol Extract Selectively Kills MDA-MB-231 Cells through ROS Generation, Sustained JNK Activation and Cell Growth and Survival Inhibition. Scientific Reports. 2019;9(1):13045. Crossref
Kontomanolis EN, Koutras A, Syllaios A, Schizas D, Mastoraki A, Garmpis N, et al. Role of Oncogenes and Tumor-suppressor Genes in Carcinogenesis: A review. Anticancer Research. 2020;40(11):6009–6015. Crossref
Speidel D. The Role of DNA Damage Responses in p53 Biology. Archives Toxicology. 2015;89(4):501–517. Crossref
Susilowati S, Anggraini TD. Efek Sitotoksisitas dan Selektivitas Fraksi Aktif Ekstrak Daun Kelor (Moringa oleifera Lamk.) terhadap Sel Kanker Payudara T47D. Farmasains: Jurnal Ilmiah Ilmu Kefarmasian. 2018;5(2):50–54. Crossref
Riwanti P, Izazih F, Amaliyah A. Pengaruh Perbedaan Konsentrasi Etanol pada Kadar Flavonoid Total Ekstrak Etanol 50, 70 dan 96% Sargassum polycystum dari Madura. Journal of Pharmaceutical Care Anwar Medika (J-PhAM). 2020;2(2):82–95. Crossref
Sair AT, Li Y, Zhao W, Li T, Liu RH. Anticancer Activity of Apple Peel Extracts Against Human Breast Cancer Cells through Insulin-Like Growth Factor-1 Signal Transduction Pathway. Journal of Agriculture and Food Research. 2023;11:100507. Crossref
Setiawan SI, Safitri EI, Muna LN, Hidayati DN. Aktivitas Sitotoksik dan Induksi Apoptosis dari Ekstrak Etanol Kulit Apel Hijau (Pyrus malus L.) terhadap Sel MCF-7. Jurnal Pharmascience. 2021;8(2):69-78. Crossref
Kalinowska M, Bielawska A, Lewandowska-Siwkiewicz H, Priebe W, Lewandowski W. Apples: Content of Phenolic Compounds vs. Variety, Part of Apple and Cultivation Model, Extraction of Phenolic Compounds, Biological Properties. Plant Physiology and Biochemistry. 2014;84:169-188. Crossref
Lin ST, Tu SH, Yang PS, Lee WH, Ho CT, Wu CH, et al. Apple Polyphenol Phloretin Inhibits Colorectal Cancer Cell Growth via Inhibition of The Type 2 Glucose Transporter and Activation of p53-Mediated Signaling. Journal of Agricultural and Food Chemistry. 2016;64(36):6826-6837. Crossref
Nezbedova L, McGhie T, Christensen M, Heyes J, Nasef NA, Mehta S. Onco-Preventive and Chemo-Protective Effects of Apple Bioactive Compounds. Nutrients. 2021;13(11):4025. Crossref
Eff ARY. In-vitro Cytotoxic Assay 50% Ethanol Extract Kitolod (Isotoma longiflora (L.) Presl.) Leaf Against Cervical Cancer Cells (Ca Ski Cell Line). Farmasains: Jurnal Ilmiah Ilmu Kefarmasian. 2016;3(1):7–12.
Authors
Adhitya, B. H. and Nisa, D. N. H. (2025) “Cytotoxicity and Antiproliferative Activities of Ethanolic Peel Extract of Pyrus malus L. on T47D Cells”, Farmasains : Jurnal Ilmiah Ilmu Kefarmasian, 12(2), pp. 56–63. doi: 10.22236/farmasains.v12i2.18385.
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