Main Article Content
Abstract
Background: Cancer is a complex disease characterized by dysregulated cell growth and the potential to invade surrounding tissues. Current therapeutic approaches continue to expand, including increasing interest in bioactive compounds derived from natural products. This study aims to evaluate the biological activity of ethanol, n-hexane, and ethyl acetate fractions of Hylocereus undatus (white dragon fruit) peel extract against the HeLa cervical cancer cell line.
Method: The extraction process was performed using the maceration method, and phytochemical screening was conducted using stain reagents. The cytotoxicity test was carried out using the MTT assay with concentrations of 1000, 500, 250, 125, 62.5, and 31.25 µg/mL, while morphological changes were observed under an inverted microscope.
Results: The phytochemical screening indicated that alkaloids, steroids, and triterpenoids were present in the n-hexane fraction; flavonoids and tannins in the ethanol fraction; and flavonoids, alkaloids, and tannins in the ethyl acetate fraction. The highest IC50 value (311.27 µg/mL) was observed on the n-hexane fraction compared to the other fractions. The HeLa cell line showed shrinkage after treatment with all fractions.
Conclusion: Of the three tested fractions, cytotoxicity was observed solely in the n-hexane fraction, whereas the ethyl acetate and ethanol fractions remained inactive against HeLa cells.
Keywords
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Copyright (c) 2026 Annisa Krisridwany, Sindi Novita Sari, Aji Winanta, Perdana Priya Heresmita, Rifki Febriansah

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References
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- Ben, I.O. et al. (2013) “Preliminary Phytochemical Screening and In vitro Antioxidant Properties of Trichilia monadelpha (Thonn.) J. J. de Wilde (Meliaceae),” Journal of Medical and Biomedical Sciences, 2(2), pp. 6–15.
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- Bray, F. et al. (2024) “Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,” CA: A Cancer Journal for Clinicians, 74(3), pp. 229–263. Available at: https://doi.org/10.3322/caac.21834.
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- Fauzi, N.N. and Maryati (2017) Uji Sitotoksik Ekstrak Etanol Kulit Buah Naga Merah (Hylocereus polyrhizus) dan Kulit Buah Naga Putih (Hylocereus undatus) Terhadap Sel Kanker Payudara MCF-7. Bachelor Thesis. Universitas Muhammadiyah Surakarta.
- Fernandes, P.A., Silva, D.A. e and Lima, M.A. (2015) “Cytotoxic effects of alkaloids on cervical carcinoma cell lines: a review,” Revista de Ciências Farmacêuticas Básica e Aplicada, 36(3). Available at: http://200.145.71.41/index.php/ojs/article/view/23 (Accessed: March 19, 2025).
- Ferreres, F. et al. (2017) “Optimization of the recovery of high-value compounds from pitaya fruit by-products using microwave-assisted extraction,” Food Chemistry, 230, pp. 463–474. Available at: https://doi.org/10.1016/j.foodchem.2017.03.061.
- Geran, R., S. et al. (1972) “Protocols for Screening Chemical Agents and Natural Products against Animal Tumors and Other Biological Systems.,” Cancer Chemotherapy Reports, 13.
- Gusungi, D.E. et al. (2020) “Studi Aktivitas Antioksidan Dan Antikanker Payudara (MCF-7) Ekstrak Etanol Daun Benalu Langsat Dendrophthoe pentandra,” Biofarmasetikal Tropis (The Tropical Journal of Biopharmaceutical), 3(1), pp. 166–174. Available at: https://doi.org/10.55724/j.biofar.trop.v3i1.274.
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- Jan, N.U. et al. (2022) “Antioxidant and Cytotoxic activity of Steroidal Alkaloids Isolated from Sarcococca saligna against DPPH and HeLa Cell Lines,” Indian Journal of Pharmaceutical Education and Research, 56(2), pp. 489–496. Available at: https://doi.org/10.5530/ijper.56.2.70.
- Jeronimo, M.C., Orsine, J.V.C. and Novaes, M.R.C.G. (2017) “Nutritional pharmacological and toxicological characteristics of pitaya (Hylocereus undatus): A review of the literature,” African Journal of Pharmacy and Pharmacology, 11(27), pp. 300–304. Available at: https://doi.org/10.5897/AJPP2016.4582.
- Khoo, H.E. et al. (2022) “Betacyanins and Anthocyanins in Pulp and Peel of Red Pitaya (Hylocereus polyrhizus cv. Jindu), Inhibition of Oxidative Stress, Lipid Reducing, and Cytotoxic Effects,” Frontiers in Nutrition, 9. Available at: https://doi.org/10.3389/fnut.2022.894438.
- Khotimah, T.K. et al. (2021) “Antibacterial Activity of Fractions from Extract Ethanolic of Hylocereus polyrhizus Peel Against E. coli and S. aureus,” Journal of Fundamental and Applied Pharmaceutical Science, 1(2), pp. 65–71. Available at: https://doi.org/10.18196/jfaps.v1i2.11001.
- Korukola, N. et al. (2023) “Exploration of in vitro Antioxidant and Cytotoxic Activities of Whole Plant Extracts of Rhynchosia heynei Wight & Arn: An Endemic Medicinal Herbaceous Under Shrub of Eastern Ghats of India,” Asian Journal of Chemistry, 35(7), pp. 1702–1706. Available at: https://doi.org/10.14233/ajchem.2023.27955.
- Kristina, S.A., Endarti, D. and Aditama, H. (2022) “Prediction of Productivity Costs Related to Cervical Cancer Mortality in Indonesia 2018,” The Malaysian Journal of Medical Sciences : MJMS, 29(1), pp. 138–144. Available at: https://doi.org/10.21315/mjms2022.29.1.13.
- Lin, X. et al. (2021) “Comparative Metabolic Profiling in Pulp and Peel of Green and Red Pitayas (Hylocereus polyrhizus and Hylocereus undatus) Reveals Potential Valorization in the Pharmaceutical and Food Industries,” BioMed Research International, 2021(1), p. 6546170. Available at: https://doi.org/10.1155/2021/6546170.
- Luo, H. et al. (2014) “Chemical composition and in vitro evaluation of the cytotoxic and antioxidant activities of supercritical carbon dioxide extracts of pitaya (dragon fruit) peel,” Chemistry Central Journal, 8(1). Available at: https://doi.org/10.1186/1752-153X-8-1.
- Madane, P. et al. (2020) “Dragon fruit (Hylocereus undatus) peel as antioxidant dietary fibre on quality and lipid oxidation of chicken nuggets,” Journal of Food Science and Technology, 57(4), pp. 1449–1461. Available at: https://doi.org/10.1007/s13197-019-04180-z.
- Modarresi Chahardehi, A. et al. (2021) “Low cytotoxicity, and antiproliferative activity on cancer cells, of the plant Senna alata (Fabaceae),” Revista de Biología Tropical, 69(1). Available at: https://doi.org/10.15517/rbt.v69i1.42144.
- Padmavathy, K. et al. (2021) “Phytochemical Profiling and Anticancer Activity of Dragon Fruit Hylocereus Undatus Extracts Against Human Hepatocellular Carcinoma Cancer (Hepg-2) Cells,” International Journal Of Pharmaceutical Sciences And Research, 12(5).
- S. Eldeen, I. et al. (2020) “Regulation of pro-inflammatory enzymes by the dragon fruits from Hylocereus undatus (Haworth) and squalene - its major volatile constituents,” Pharmacognosy Magazine, 16(68), p. 81. Available at: https://doi.org/10.4103/pm.pm_271_19.
- Sajjadi, S.E. et al. (2015) “Cytotoxic effect of Cousinia verbascifolia Bunge against OVCAR-3 and HT-29 cancer cells,” Journal of Herbmed Pharmacology, 4(1), pp. 15–19.
- WHO, I.A. for R. on C. (2021) Global Cancer Observatory, Indonesia.
- Winanta, A., Hanik, L.S. and Febriansah, R. (2021) “Antioxidant Activity and Cytotoxic Potential of Parijoto (Medinilla speciosa (Reinw ex BL)) Fruit Fractions on HeLa Cell Line,” Indonesian Journal of Cancer Chemoprevention, 12(2), p. 74. Available at: https://doi.org/10.14499/indonesianjcanchemoprev12iss2pp74-82.
- Zain, N.M., Nazeri, M.A. and Azman, N.A. (2019) “Assessment on Bioactive Compounds and The Effect of Microwave on Pitaya Peel,” Jurnal Teknologi (Sciences & Engineering), 81(2). Available at: https://doi.org/10.11113/jt.v81.12847.
References
Amna, U. et al. (2019) “Evaluation of cytotoxic activity from Temurui (Murraya koenigii [Linn.] Spreng) leaf extracts against HeLa cell line using MTT assay,” Journal of Advanced Pharmaceutical Technology & Research, 10(2), p. 51. Available at: https://doi.org/10.4103/japtr.JAPTR_373_18.
Ben, I.O. et al. (2013) “Preliminary Phytochemical Screening and In vitro Antioxidant Properties of Trichilia monadelpha (Thonn.) J. J. de Wilde (Meliaceae),” Journal of Medical and Biomedical Sciences, 2(2), pp. 6–15.
Bhatla, N. et al. (2021) “Cancer of the cervix uteri: 2021 update,” International Journal of Gynecology & Obstetrics, 155(S1), pp. 28–44. Available at: https://doi.org/10.1002/ijgo.13865.
Bray, F. et al. (2024) “Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,” CA: A Cancer Journal for Clinicians, 74(3), pp. 229–263. Available at: https://doi.org/10.3322/caac.21834.
Cruz, V. et al. (2022) “Characterization and assessment of phytochemical properties of dragon fruit (Hylocereus undatus and Hylocereus polyrhizus) peels,”, International Journal of Agricultural Technology, 18(3), pp. 1307-1318
Desai, N.M. and Nikam, V.K. (2024) “Analysis and Phytochemical Screening of the Polyphenolic Antioxidant Activity of the White Dragon Fruit (Hylocereus undatus),” Research Journal of Phytochemistry, 18(1), pp. 13–19. Available at: https://doi.org/10.3923/rjp.2023.13.19.
El-Nashar, H.A.S. et al. (2024) “HPLC-ESI/MS-MS metabolic profiling of white pitaya fruit and cytotoxic potential against cervical cancer: Comparative studies, synergistic effects, and molecular mechanistic approaches,” Journal of Pharmaceutical and Biomedical Analysis, 244. Available at: https://doi.org/10.1016/j.jpba.2024.116121.
Fauzi, N.N. and Maryati (2017) Uji Sitotoksik Ekstrak Etanol Kulit Buah Naga Merah (Hylocereus polyrhizus) dan Kulit Buah Naga Putih (Hylocereus undatus) Terhadap Sel Kanker Payudara MCF-7. Bachelor Thesis. Universitas Muhammadiyah Surakarta.
Fernandes, P.A., Silva, D.A. e and Lima, M.A. (2015) “Cytotoxic effects of alkaloids on cervical carcinoma cell lines: a review,” Revista de Ciências Farmacêuticas Básica e Aplicada, 36(3). Available at: http://200.145.71.41/index.php/ojs/article/view/23 (Accessed: March 19, 2025).
Ferreres, F. et al. (2017) “Optimization of the recovery of high-value compounds from pitaya fruit by-products using microwave-assisted extraction,” Food Chemistry, 230, pp. 463–474. Available at: https://doi.org/10.1016/j.foodchem.2017.03.061.
Geran, R., S. et al. (1972) “Protocols for Screening Chemical Agents and Natural Products against Animal Tumors and Other Biological Systems.,” Cancer Chemotherapy Reports, 13.
Gusungi, D.E. et al. (2020) “Studi Aktivitas Antioksidan Dan Antikanker Payudara (MCF-7) Ekstrak Etanol Daun Benalu Langsat Dendrophthoe pentandra,” Biofarmasetikal Tropis (The Tropical Journal of Biopharmaceutical), 3(1), pp. 166–174. Available at: https://doi.org/10.55724/j.biofar.trop.v3i1.274.
Hutomo, S. et al. (2017) “Perubahan morfologi sel HeLa setelah paparan ekstrak etanolik Curcuma longa,” Majalah Kedokteran Gigi Indonesia, 2(1), pp. 1–5. Available at: https://doi.org/10.22146/majkedgiind.11248.
Jan, N.U. et al. (2022) “Antioxidant and Cytotoxic activity of Steroidal Alkaloids Isolated from Sarcococca saligna against DPPH and HeLa Cell Lines,” Indian Journal of Pharmaceutical Education and Research, 56(2), pp. 489–496. Available at: https://doi.org/10.5530/ijper.56.2.70.
Jeronimo, M.C., Orsine, J.V.C. and Novaes, M.R.C.G. (2017) “Nutritional pharmacological and toxicological characteristics of pitaya (Hylocereus undatus): A review of the literature,” African Journal of Pharmacy and Pharmacology, 11(27), pp. 300–304. Available at: https://doi.org/10.5897/AJPP2016.4582.
Khoo, H.E. et al. (2022) “Betacyanins and Anthocyanins in Pulp and Peel of Red Pitaya (Hylocereus polyrhizus cv. Jindu), Inhibition of Oxidative Stress, Lipid Reducing, and Cytotoxic Effects,” Frontiers in Nutrition, 9. Available at: https://doi.org/10.3389/fnut.2022.894438.
Khotimah, T.K. et al. (2021) “Antibacterial Activity of Fractions from Extract Ethanolic of Hylocereus polyrhizus Peel Against E. coli and S. aureus,” Journal of Fundamental and Applied Pharmaceutical Science, 1(2), pp. 65–71. Available at: https://doi.org/10.18196/jfaps.v1i2.11001.
Korukola, N. et al. (2023) “Exploration of in vitro Antioxidant and Cytotoxic Activities of Whole Plant Extracts of Rhynchosia heynei Wight & Arn: An Endemic Medicinal Herbaceous Under Shrub of Eastern Ghats of India,” Asian Journal of Chemistry, 35(7), pp. 1702–1706. Available at: https://doi.org/10.14233/ajchem.2023.27955.
Kristina, S.A., Endarti, D. and Aditama, H. (2022) “Prediction of Productivity Costs Related to Cervical Cancer Mortality in Indonesia 2018,” The Malaysian Journal of Medical Sciences : MJMS, 29(1), pp. 138–144. Available at: https://doi.org/10.21315/mjms2022.29.1.13.
Lin, X. et al. (2021) “Comparative Metabolic Profiling in Pulp and Peel of Green and Red Pitayas (Hylocereus polyrhizus and Hylocereus undatus) Reveals Potential Valorization in the Pharmaceutical and Food Industries,” BioMed Research International, 2021(1), p. 6546170. Available at: https://doi.org/10.1155/2021/6546170.
Luo, H. et al. (2014) “Chemical composition and in vitro evaluation of the cytotoxic and antioxidant activities of supercritical carbon dioxide extracts of pitaya (dragon fruit) peel,” Chemistry Central Journal, 8(1). Available at: https://doi.org/10.1186/1752-153X-8-1.
Madane, P. et al. (2020) “Dragon fruit (Hylocereus undatus) peel as antioxidant dietary fibre on quality and lipid oxidation of chicken nuggets,” Journal of Food Science and Technology, 57(4), pp. 1449–1461. Available at: https://doi.org/10.1007/s13197-019-04180-z.
Modarresi Chahardehi, A. et al. (2021) “Low cytotoxicity, and antiproliferative activity on cancer cells, of the plant Senna alata (Fabaceae),” Revista de Biología Tropical, 69(1). Available at: https://doi.org/10.15517/rbt.v69i1.42144.
Padmavathy, K. et al. (2021) “Phytochemical Profiling and Anticancer Activity of Dragon Fruit Hylocereus Undatus Extracts Against Human Hepatocellular Carcinoma Cancer (Hepg-2) Cells,” International Journal Of Pharmaceutical Sciences And Research, 12(5).
S. Eldeen, I. et al. (2020) “Regulation of pro-inflammatory enzymes by the dragon fruits from Hylocereus undatus (Haworth) and squalene - its major volatile constituents,” Pharmacognosy Magazine, 16(68), p. 81. Available at: https://doi.org/10.4103/pm.pm_271_19.
Sajjadi, S.E. et al. (2015) “Cytotoxic effect of Cousinia verbascifolia Bunge against OVCAR-3 and HT-29 cancer cells,” Journal of Herbmed Pharmacology, 4(1), pp. 15–19.
WHO, I.A. for R. on C. (2021) Global Cancer Observatory, Indonesia.
Winanta, A., Hanik, L.S. and Febriansah, R. (2021) “Antioxidant Activity and Cytotoxic Potential of Parijoto (Medinilla speciosa (Reinw ex BL)) Fruit Fractions on HeLa Cell Line,” Indonesian Journal of Cancer Chemoprevention, 12(2), p. 74. Available at: https://doi.org/10.14499/indonesianjcanchemoprev12iss2pp74-82.
Zain, N.M., Nazeri, M.A. and Azman, N.A. (2019) “Assessment on Bioactive Compounds and The Effect of Microwave on Pitaya Peel,” Jurnal Teknologi (Sciences & Engineering), 81(2). Available at: https://doi.org/10.11113/jt.v81.12847.
