Antiproliferative potential of the essential oil of Origanum majorana Linn. in melanoma cells and intracellular effects on neoplastic and non-neoplastic cells
Keywords:Flow cytometry; Cancer; Cytotoxicity; Melanoma; Marjoram.
The objectives of this study were to evaluate the intracellular activity of the essential oil of Origanum majorana (MARJ) in Madin Darby Bovine Kidney (MDBK) and murine metastatic melanoma (B16F10) and elucidate your chemical composition. Through flow cytometry parameters were analyzed membrane fluidity (F), reactive oxygen species (ROS), DNA fragmentation index (IFD), mitochondrial membrane potential (MMP), cell cycle, plasma membrane lipoperoxidation (LPO), cell viability, necrosis and apoptosis of cell lines treated with MARJ at concentrations of 0.25, 0.5 and 1 mg/mL for 24 hours. The composition of MARJ was determined by gas chromatography, and its major components were terpenes: hydrated cis-sabinene, 4-terpineol and gamma-terpinene. The results showed that all MARJ concentrations reduced ROS, LPO and S phase cells of the MDBK lineage. In B16F10 cells, MARJ treatments reduced ROS and cells in G2 phase, increasing cells in S phase. Concentrations of 0.5 and 1 mg/mL caused a reduction in F and 0.5 mg/mL increased the MMP in the MDBK lineage, while LPO was reduced at the concentration of 0.5 mg/mL in the B16F10 cells. The results of the evaluations of ROS production, plasma membrane integrity and LPO indicated antioxidant activity in the cells studied. Through cell cycle analysis, it was possible to observe that MARJ exerted an antiproliferative effect on melanoma cells, being able to interrupt the multiplication of this cell type.
Abdel-Massih, R. M., Fares, R., Bazzi, S., El-Chami, N., & Baydoun, E. (2010). The apopitotic and anti-proliferative activity of Origanum majorana extracts on human leukemic cell line. Leukemia Research, 34, 1052-1056.
American Cancer Society. Cancer facts & figures 2021 – Skin. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2021.html
Arathi, B. P, Sowmya, P. R., Kuriakose, G. C., Vijay, K., Baskaran, V., Jayabaskaran, C., & Lakshminarayana, R. (2016). Enhanced cytotoxic and apoptosis inducing activity of lycopene oxidation products in different cancer cell lines. Food and Chemical Toxicology, 97, 265-276.
Balusamy, S. R., Perumalsamy, H., Huq, M. A., & Balasubramanian, B. (2018). Anti-proliferative activity of Origanum vulgare inhibited lipogenesis and induced mitochondrial mediated apoptosis in human stomach cancer cell lines. Biomedicine and pharmacotherapy, 108, 1835-1844.
Bayala, B., Bassole, I. H. N., Scifo, R., Gnoula, C., Morel, L., Lobaccaro, J. M. A., & Simpore, J. (2014). Anticancer activity of essential oils and their chemical components - a review. American Journal of Cancer Research, 4(6), 591-607.
Brandão, H. N., David, J. P., Couto, R. D., Nascimento, J. A. P., & David, J. M. (2010). Química e farmacologia de quimioterápicos antineoplásicos derivados de plantas. Química Nova, 33(1), 1359 -1369.
Brasil. (1988). Farmacopéia Brasileira - Volume 1. Agência Nacional de Vigilância Sanitária.
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, (2018). A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), 394-424.
Del Ré, P. V. & Jorge, N. (2012). Especiarias como antioxidantes naturais: aplicações em alimentos e implicação na saúde. Revista Brasileira de Plantas Medicinais, 14(2), 389-399.
Dhaheri, Y. A., Attoub, S., Arafat, K., Abuqamar, S., Viallet, J., Saleh, A., Agha, H. A., Eid, A., & Iratni, R. (2013). Anti-Metastatic and Anti-Tumor Growth Effects of Origanum majorana on Highly Metastatic Human Breast Cancer Cells: Inhibition of NFκB Signaling and Reduction of Nitric Oxide Production. PLoS One, 8(7).
Domínguez-Rebolledo, A. E., Martínez-Pastor, F., Bisbal, A. F., Ros-Santaella, J. L, García-Álvarez, O., Maroto-Morales, A., Soler, A. J., Garde, J. J., & Fernández-Santos, M. R. (2010). Response of thawed epididymal red deer spermatozoa to increasing concentrations of hydrogenperoxide, and importance of individual male variability. Reproduction in Domestic Animals, 46, 393-403.
El-Ashmawy, I. M., Saleh, A., & Salama, O. M. (2007). Effects of Marjoram Volatile Oil and Grape Seed Extract on Ethanol Toxicity in Male Rats. Basic & Clinical Pharmacology & Toxicology, 101, 320-327.
Erdogan. A. & Ozkan, A. (2017). Investigatıon of Antioxıdative, Cytotoxic, Membrane-Damaging and Membrane-Protective Effects of the Essentıal Oil of Origanum majorana and its Oxygenated Monoterpene Component Linalool in Human-Derived Hep G2 Cell Line. Iranian Journal of Pharmaceutical Research, 16, 24-34.
Evenson, D. & Jost, L. (1994). Sperm chromatin structure assay: DNA denaturability. Methods in Cell Biology, 42, 159-176.
Fitzmaurice, C., Allen, C., & Barber, R. M. (2018). Global, Regional, and National Cancer Incidence,Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. Journal of American Medical Association Oncology, 3(4), 524-548.
Goldschmidt, M. H., & Hendrick, M. J. (2002). Tumors of the Skin and Soft Tissues. In: Meuten, D.J. Tumors in Domestic Animals. 4 ed. Iowa: Iowa State Press.
Greay, S. J., Ireland, D. J., Kissick, H. T., Levy, A., Beilharz, M. W., Riley, T. V., & Carson, C. F. (2010). Induction of necrosis and cell cycle arrest in murine cancer cell lines by Melaleuca alternifolia (tea tree) oil and terpinen-4-ol. Cancer Chemotherapy Pharmacology, 65, 877–888.
Habibi, E., Shokrzadeh, M., Chabra, A., Naghshvar, F., Keshavarz-Maleki, R., & Ahmadi, A. (2014). Protective effects of Origanum vulgare ethanol extract against cyclophosphamide-induced liver toxicity in mice. Pharmaceutical Biology, 53(1), 1-6.
Hajlaoui, H., Mighri, H., Aouni, M., Gharsallah, N., & Kadri, A. (2016). Chemical composition and in vitro evaluation of antioxidant, antimicrobial, cytotoxicity and anti-acetylcholinesterase properties of Tunisian Origanum majorana L. essential oil. Microbial Pathogenesis, 95, 86-94.
Instituto Nacional do Câncer - Estimativa 2018: incidência de câncer no Brasil. (2017). Instituto Nacional de Câncer José Alencar Gomes da Silva. Coordenação de Prevenção e Vigilância. Rio de Janeiro: INCA.
Khan, M. S. A., Ahmad, I., & Cameotra, S. S. (2014). Carum copticum and Thymus vulgaris oils inhibit virulence in Trichophyton rubrum and Aspergillus spp. Brazilian Journal of Microbiology, 45(2), 523-531.
Mendanha, S. A., Moura, S. S., Anjos, J. L. V., Valadares, M. C., & Alonso, A. (2013). Toxicity of terpenes on fibroblast cells compared to their hemolytic potential and increase in erythrocyte membrane fluidity. Toxicology in Vitro, 27, 323-329.
Nanni, V., Di Marco, G., Sachetti, G., Canini, A., & Gismondi, A. (2020). Oregano Phytocomplex Induces Programmed Cell Death in Melanoma Lines via Mitochondria and DNA Damage. Foods, 9, 1-27.
Petrunkina, A. M., & Harrison, R. A. (2013) Fluorescence technologies for evaluating male gamete (dys) function. Reproduction in Domestic Animals, 48, 11-24.
Pereira A. S., Shitsuka, D. M., Parreira, F. J. & Sitsuka, R. (2018). Metodologia da pesquisa científica. UFSM.
Ramadan, G., El-Beih, N. M., & Zahra, M. M. (2012). Egyptian sweet marjoram leaves protect against genotoxicity, immunosuppression and other complications induced by cyclophosphamide in albino rats. British Journal of Nutrition, 108, 1059–1068.
Sharma, M., Agrawal, S. K., Sharma, P. R., Chadha, B. S., Khosla, M. K., & Saxena, A. K. (2010). Cytotoxic and apoptotic activity of essential oil from Ocimum viride towards COLO 205 cells. Food and Chemical Toxicology, 48, 336–344.
Silva, C. S. 2016. Estudo retrospectivo de melanomas cutâneos caninos e determinação da atividade citotóxica de produtos vegetais frente a células neoplásicas (B16F10) e não neoplásicas (MDBK). 2016. 88f. Dissertação (Mestrado) – Programa de Pós-Graduação em Veterinária – Universidade Federal de Pelotas – Pelotas.
Silva, C. S., Guim, T. N., Fernandes, C. G., Barboza, D. V., & Cleff, M. B. Estudo retrospectivo de melanomas cutâneos em cães. (2017). Clínica Veterinária, 22(126), 52-60.
Silva, E. C. B., Cajueiro, J. F. P., Silva, S. V., Soares, V. P., & Guerra, M. M. P. (2012). Effect of antioxidants resveratrol and quercetin on in vitro evaluation of frozen ram sperm. Theriongelonogy, 77, 1722-1726.
Soliman, A. M., Desouky, S., Marzouk, M., & Sayed, A. A. (2016). Origanum majorana Attenuates Nephrotoxicity of Cisplatin Anticancer Drug through Ameliorating Oxidative Stress. Nutrients, 8(264), 1-9.
Tatman, D., & Mo, H. (2002). Volatile isoprenoid constituents of fruits, vegetables and herbs cumulatively suppress the proliferation of murine B16 melanoma and human HL-60 leukemia cells. Cancer Lettters, 175, 129-139.
Waller, S. B., Cleff, M. B., Mattos, C. B., Silva, C. C., Giordani, C., Lana, D. F. D., Fuentefria, A. M., Freitag, R. A., Sallis, E. S. V., Mello, J. R. B., Faria, R. O., & Meireles, M. C. A. (2019). In vivo protection of the marjoram (Origanum majorana Linn.) essential oil in the cutaneous sporotrichosis by Sporothrix brasiliensis. Natural Product and Research, 17, 1-5.
Weyden, L., Brenn, T., Patton, E. E., Wood, G. A., & Adams, D. J. (2020). Spontaneously occurring melanoma in animals and their relevance to human melanoma. The Journal of Pathology, 252(1), 4-21.
Xu, W. & Macarthur, G. (2016). Cell Cycle Regulation and Melanoma. Current Oncology Reports, 18, 1-12.
Zuccari, D. A. P. C., Jardim-Perassi, B. V., Lopes, J. R., Colombo, J., & Silva, C. L. (2016). Biologia do Câncer. In: Daleck, C. R., De Nardi, A. B. Oncologia em Cães e Gatos. Roca.
How to Cite
Copyright (c) 2021 Cristine Cioato da Silva; Claudia Giordani; Tony Picoli; Karina Affeldt Guterres; Soliane Carra Perera; Gabriela Almeida Capella; Stefanie Bressan Waller; Carine Dahl Corcini; Antonio Sergio Varela Junior; Rogério Antonio Freitag; Geferson Fischer; Marlete Brum Cleff
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.