Effect of 2-methoxyestradiol treatment on early- and late-stage breast cancer progression in a mouse model

dc.contributor.authorPeta, Kimberly Thando
dc.contributor.authorDurandt, Chrisna
dc.contributor.authorVan Heerden, Marlene B.
dc.contributor.authorJoubert, Anna Margaretha
dc.contributor.authorPepper, Michael Sean
dc.contributor.authorAmbele, Melvin Anyasi
dc.contributor.emailmelvin.ambele@up.ac.zaen_US
dc.date.accessioned2024-04-24T04:50:22Z
dc.date.available2024-04-24T04:50:22Z
dc.date.issued2023-10
dc.descriptionDATA AVAILABILITY STATEMENT : The data supporting the results cited in the text can be found in the relevant articles cited in the references.en_US
dc.description.abstractThe prevalence of breast cancer (BC) continues to increase and is the leading cause of cancer deaths in many countries. Numerous in vitro and in vivo studies have demonstrated that 2‐methoxyestradiol (2‐ME) has antiproliferative and antiangiogenic effects in BC, thereby inhibiting tumour growth and metastasis. We compared the effect of 2‐ME in early‐ and late‐stage BC using a transgenic mouse model— FVB/N‐Tg(MMTV‐PyVT)—of spontaneously development of aggressive mammary carcinoma with lung metastasis. Mice received 100 mg/kg 2‐ME treatment immediately when palpable mammary tumours were identified (early‐stage BC; Experimental group 1) and 28 days after palpable mammary tumours were detected (late‐stage BC; Experimental group 2). 2‐ME was administered via oral gavage three times a week for 28 days after initiation of treatment, whereas control mice received the vehicle containing 10% dimethyl sulfoxide and 90% sunflower oil for the same duration as the treatment group. Mammary tumours were measured weekly over the 28 days and at termination, blood, mammary and lung tissue were collected for analysis. Mice with a tumour volume threshold of 4000mm3 were killed before the treatment regime was completed. 2‐ME treatment of early‐stage BC led to lower levels of mammary tumour necrosis, whereas tumour mass and volume were increased. Additionally, necrotic lesions and anti‐inflammatory CD163‐expressing cells were more frequent in pulmonary metastatic tumours in this group. In contrast, 2‐ME treatment of late‐stage BC inhibited tumour growth over the 28‐day period and resulted in increased CD3+ cell number and tumour necrosis. Furthermore, 2‐ME treatment slowed down pulmonary metastasis but did not increase survival of late‐stage BC mice. Besides late‐stage tumour necrosis, none of the other results were statistically significant. This study demonstrates that 2‐ME treatment has an antitumour effect on late‐stage BC, however, with no increase in survival rate, whereas the treatment failed to demonstrate any benefit in early‐stage BC.en_US
dc.description.departmentImmunologyen_US
dc.description.departmentOral Pathology and Oral Biologyen_US
dc.description.departmentPhysiologyen_US
dc.description.librarianam2024en_US
dc.description.sdgSDG-03:Good heatlh and well-beingen_US
dc.description.sponsorshipThe South African Medical Research Council Self‐Initiated Research Grant, the National Research Foundation Competitive Support for Unrated Researchers, the South African Medical Research Council University Flagship Project, the SAMRC Extramural Unit for Stem Cell Research and Therapy and the Institute for Cellular and Molecular Medicine of the University of Pretoria.en_US
dc.description.urihttp://wileyonlinelibrary.com/journal/cbfen_US
dc.identifier.citationPeta, K.T., Durandt, C., Van Heerden, M.B., Joubert, A.M., Pepper, M.S. & Ambele, M.A. Effect of 2‐methoxyestradiol treatment on early‐ and late‐stage breast cancer progression in a mouse model. Cell Biochemistry and Function 2023; 41: 898‐911. DOI:10.1002/cbf.3842.en_US
dc.identifier.issn0263-6484 (print)
dc.identifier.issn1099-0844 (online)
dc.identifier.other10.1002/cbf.3842
dc.identifier.urihttp://hdl.handle.net/2263/95734
dc.language.isoenen_US
dc.publisherWileyen_US
dc.rights© 2023 The Authors. This is an open access article under the terms of the Creative Commons Attribution License.en_US
dc.subject2‐Methoxyestradiolen_US
dc.subjectBreast canceren_US
dc.subjectIn vivoen_US
dc.subjectMetastasisen_US
dc.subjectTumour growthen_US
dc.subjectSDG-03: Good health and well-beingen_US
dc.titleEffect of 2-methoxyestradiol treatment on early- and late-stage breast cancer progression in a mouse modelen_US
dc.typeArticleen_US

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