Cytotoxic Activity of Melaleuca sp. and Eucalyptus sp. Essential Oils Against Breast Cancer MCF-7 Cells and Their Potential Role in Chemotherapy

Sukma Diani Putri; Ike Puspitaningrum; Sally Yustinawati Suryatna

doi:10.31983/jrk.v15i1.14035

Authors

Sukma Diani Putri Politeknik Negeri Indramayu
Ike Puspitaningrum Politeknik Negeri Indramayu
Sally Yustinawati Suryatna Politeknik Negeri Indramayu

DOI:

https://doi.org/10.31983/jrk.v15i1.14035

Keywords:

Breast Cancer , Essential Oil , Eucalyptus Sp , Melaleuca Sp , MCF-7

Abstract

Breast cancer remained one of the leading causes of cancer-related deaths among women, motivating the search for effective and accessible therapeutic support. Essential oils from Melaleuca sp. and Eucalyptus sp. had been reported to contain bioactive compounds with anticancer potential. This study aimed to compare their antiproliferative effects when combined with doxorubicin on MCF-7 breast cancer cells in vitro. MCF-7 cells were seeded in 96-well plates and treated with increasing concentrations of each essential oil together with doxorubicin for 48 hours. Cell viability was assessed using the resazurin assay. Both treatments reduced cell viability in a concentration-dependent manner. The combination of Melaleuca sp. and doxorubicin showed stronger inhibition, with an IC₅₀ of 0.1576 µg/mL, while Eucalyptus sp. and doxorubicin produced an IC₅₀ of 0.7792 µg/mL. These findings suggested that Melaleuca sp. demonstrated higher potency under the tested conditions. However, the absence of a doxorubicin-only control limited the interpretation of whether the effects were synergistic or simply additive. In conclusion, Melaleuca sp. appeared to have greater potential as a supportive natural agent in breast cancer treatment. Further studies were recommended to include full drug controls and mechanistic assays to better clarify the interaction with chemotherapy.

References

Assmann, C. E., Cadoná, F. C., Bonadiman, B. da S. R., Dornelles, E. B., Trevisan, G., & Cruz, I. B. M. da. (2018). Tea tree oil presents in vitro antitumor activity on breast cancer cells without cytotoxic effects on fibroblasts and on peripheral blood mononuclear cells. Biomedicine and Pharmacotherapy, 103, 1253–1261. https://doi.org/10.1016/j.biopha.2018.04.096

Banjerdpongchai, R., & Khaw-On, P. (2013). Terpinen-4-ol induces autophagic and apoptotic cell death in human leukemic HL-60 cells. Asian Pacific Journal of Cancer Prevention, 14(12), 7537–7542. https://doi.org/10.7314/APJCP.2013.14.12.7537

Berrouet, C., Dorilas, N., Rejniak, K. A., & Tuncer, N. (2020). Comparison of Drug Inhibitory Effects (IC 50) in Monolayer and Spheroid Cultures. Bulletin of Mathematical Biology, 82(6). https://doi.org/10.1007/s11538-020-00746-7

Blowman, K., Magalhães, M., Lemos, M. F. L., Cabral, C., & Pires, I. M. (2018a). Anticancer Properties of Essential Oils and Other Natural Products. In Evidence-based Complementary and Alternative Medicine (Vol. 2018). Hindawi Limited. https://doi.org/10.1155/2018/3149362

Blowman, K., Magalhães, M., Lemos, M. F. L., Cabral, C., & Pires, I. M. (2018b). Anticancer Properties of Essential Oils and Other Natural Products. In Evidence-based Complementary and Alternative Medicine (Vol. 2018). Hindawi Limited. https://doi.org/10.1155/2018/3149362

Borotová, P., Galovičová, L., Vukovic, N. L., Vukic, M., Tvrdá, E., & Kačániová, M. (2022). Chemical and Biological Characterization of Melaleuca alternifolia Essential Oil. Plants, 11(4). https://doi.org/10.3390/plants11040558

Čmiková, N., Galovičová, L., Schwarzová, M., Vukic, M. D., Vukovic, N. L., Kowalczewski, P. Ł., Bakay, L., Kluz, M. I., Puchalski, C., & Kačániová, M. (2023). Chemical Composition and Biological Activities of Eucalyptus globulus Essential Oil. Plants, 12(5). https://doi.org/10.3390/plants12051076

Ćwiklińska-Jurkowska, M., Wiese-Szadkowska, M., Janciauskiene, S., & Paprocka, R. (2023). Disparities in Cisplatin-Induced Cytotoxicity—A Meta-Analysis of Selected Cancer Cell Lines. Molecules, 28(15). https://doi.org/10.3390/molecules28155761

Dasari, S., & Bernard Tchounwou, P. (2014). Cisplatin in cancer therapy: Molecular mechanisms of action. In European Journal of Pharmacology (Vol. 740, pp. 364–378). Elsevier. https://doi.org/10.1016/j.ejphar.2014.07.025

Hoch, C. C., Petry, J., Griesbaum, L., Weiser, T., Werner, K., Ploch, M., Verschoor, A., Multhoff, G., Bashiri Dezfouli, A., & Wollenberg, B. (2023). 1,8-cineole (eucalyptol): A versatile phytochemical with therapeutic applications across multiple diseases. In Biomedicine and Pharmacotherapy (Vol. 167). Elsevier Masson s.r.l. https://doi.org/10.1016/j.biopha.2023.115467

Huang, Y., An, M., Fang, A., Olatunji, O. J., & Eze, F. N. (2022a). Antiproliferative Activities of the Lipophilic Fraction of Eucalyptus camaldulensis against MCF-7 Breast Cancer Cells, UPLC-ESI-QTOF-MS Metabolite Profile, and Antioxidative Functions. ACS Omega, 7(31), 27369–27381. https://doi.org/10.1021/acsomega.2c02389

Huang, Y., An, M., Fang, A., Olatunji, O. J., & Eze, F. N. (2022b). Antiproliferative Activities of the Lipophilic Fraction of Eucalyptus camaldulensis against MCF-7 Breast Cancer Cells, UPLC-ESI-QTOF-MS Metabolite Profile, and Antioxidative Functions. ACS Omega, 7(31), 27369–27381. https://doi.org/10.1021/acsomega.2c02389

Joy, L., Heinrich, J., Uwe, W., Juergens, R., Juergens, L. J., & Worth, H. (2020). New Perspectives for Mucolytic, Anti-inflammatory and Adjunctive Therapy with 1,8-Cineole in COPD and Asthma: Review on the New Therapeutic Approach. Adv Ther, 37, 1737–1753. https://doi.org/10.6084/m9.figshare.11876436

Kashkoulinejad-Kouhi, T., Safarian, S., Arnaiz, B., & Saa, L. (2021). Enhancement of cisplatin sensitivity in human breast cancer MCF-7 cell line through BiP and 14-3-3ζ co-knockdown. Oncology Reports, 45(2), 665–679. https://doi.org/10.3892/or.2020.7898

Kciuk, M., Gielecińska, A., Mujwar, S., Kołat, D., Kałuzińska-Kołat, Ż., Celik, I., & Kontek, R. (2023). Doxorubicin—An Agent with Multiple Mechanisms of Anticancer Activity. In Cells (Vol. 12, Number 4). MDPI. https://doi.org/10.3390/cells12040659

Khan, H. (2025). Characterization of 1,8-Cineole (Eucalyptol) From Myrtle and its Potential Antibacterial and Antioxidant Activities. Karbala International Journal of Modern Science, 11(1), 199–207. https://doi.org/10.33640/2405-609X.3394

Lashen, A. G., Toss, M. S., Katayama, A., Gogna, R., Mongan, N. P., & Rakha, E. A. (2021). Assessment of proliferation in breast cancer: cell cycle or mitosis? An observational study. Histopathology, 79(6), 1087–1098. https://doi.org/10.1111/his.14542

Lin, C. C., Wu, C. S., Chen, Y. J., Chen, J. J. W., Shieh, J. J., Huang, C. H., Lin, P. S., Chang, G. C., & Chang, J. T. (2012). Terpinen-4-ol induces apoptosis in human nonsmall cell lung cancer in vitro and in vivo. Evidence-Based Complementary and Alternative Medicine, 2012. https://doi.org/10.1155/2012/818261

Markowski, J., & Junka, A. (2025). Multifaceted Action of 1,8-Cineole in Antibacterial and Anti-inflammatory Treatment of Respiratory Tract Diseases. Otolaryngologia Polska, 79(1), 1–5. https://doi.org/10.5604/01.3001.0054.9607

Merghni, A., Belmamoun, A. R., Urcan, A. C., Bobiş, O., & Lassoued, M. A. (2023). 1,8-Cineol (Eucalyptol) Disrupts Membrane Integrity and Induces Oxidative Stress in Methicillin-Resistant Staphylococcus aureus. Antioxidants, 12(7). https://doi.org/10.3390/antiox12071388

Mirmalek, S. A., Jangholi, E., Jafari, M., Yadollah-Damavandi, S., Javidi, M. A., Parsa, Y., Parsa, T., Salimi-Tabatabaee, S. A., Kolagar, H. G., Jalil, S. K., & Alizadeh-Navaei, R. (2016). Comparison of in vitro cytotoxicity and apoptogenic activity of magnesium chloride and cisplatin as conventional chemotherapeutic agents in the MCF-7 cell line. Asian Pacific Journal of Cancer Prevention, 17, 131–134. https://doi.org/10.7314/APJCP.2016.17.S3.131

Putri, S. D., Puspitaningrum, I., & Suryatna, S. Y. (2023). Efektivitas Eucalyptus sp sebagai Disinfektan Spray terhadap Staphylococcus aureus. Al-Asalmiya Nursing, (2). https://jurnal.ikta.ac.id/index.php/keperawatan/

Rodenak-Kladniew, B., Castro, M. A., Crespo, R., Galle, M., & García de Bravo, M. (2020). Anti-cancer mechanisms of linalool and 1,8-cineole in non-small cell lung cancer A549 cells. Heliyon, 6(12). https://doi.org/10.1016/j.heliyon.2020.e05639

Sánchez-Díez, M., Romero-Jiménez, P., Alegría-Aravena, N., Gavira-O’Neill, C. E., Vicente-García, E., Quiroz-Troncoso, J., González-Martos, R., Ramírez-Castillejo, C., & Pastor, J. M. (2025). Assessment of Cell Viability in Drug Therapy: IC50 and Other New Time-Independent Indices for Evaluating Chemotherapy Efficacy. Pharmaceutics, 17(2). https://doi.org/10.3390/pharmaceutics17020247

Sharma, M., Grewal, K., Jandrotia, R., Batish, D. R., Singh, H. P., & Kohli, R. K. (2022). Essential oils as anticancer agents: Potential role in malignancies, drug delivery mechanisms, and immune system enhancement. In Biomedicine and Pharmacotherapy (Vol. 146). Elsevier Masson s.r.l. https://doi.org/10.1016/j.biopha.2021.112514

Shiekh, R. A. E., Atwa, A. M., Elgindy, A. M., Mustafa, A. M., Senna, M. M., Alkabbani, M. A., & Ibrahim, K. M. (2025). Therapeutic applications of eucalyptus essential oils. In Inflammopharmacology (Vol. 33, Number 1, pp. 163–182). Springer Science and Business Media Deutschland GmbH. https://doi.org/10.1007/s10787-024-01588-8

Tacar, O., Sriamornsak, P., & Dass, C. R. (2013). Doxorubicin: An update on anticancer molecular action, toxicity and novel drug delivery systems. In Journal of Pharmacy and Pharmacology (Vol. 65, Number 2, pp. 157–170). https://doi.org/10.1111/j.2042-7158.2012.01567.x

Thalappil, M. A., Singh, P., Carcereri de Prati, A., Sahoo, S. K., Mariotto, S., & Butturini, E. (2024). Essential oils and their nanoformulations for breast cancer therapy. In Phytotherapy Research (Vol. 38, Number 2, pp. 556–591). John Wiley and Sons Ltd. https://doi.org/10.1002/ptr.8054

Zhou, L. J., Li, F. R., Huang, L. J., Yang, Z. R., Yuan, S., & Bai, L. H. (2016). Antifungal activity of Eucalyptus oil against rice blast fungi and the possible mechanism of gene expression pattern. Molecules, 21(5). https://doi.org/10.3390/molecules21050621