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Ethanolic extract of Euphorbia royleana Boiss. reduces metastasis of breast cancer cells and inhibits tumor progression in vivo

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Abstract

Metastasis is the most devastating attribute of breast cancer (BC) that leads to high mortality. It is a complex process of tumor cell migration, invasion, and angiogenesis. In this study, we evaluated the effect of ERA on BC metastasis and BC progression in vivo. The transwell invasion/migration and wound healing assays showed that ERA treatment significantly reduced the invasion and migration of BC cell lines. The expression of mesenchymal (E-cadherin and N-cadherin), matrix metalloproteinases (MMP2, MMP9), and stemness markers (Oct3) were down-regulated by ERA. Furthermore, ERA down-regulated angiogenic chemokines (CXCL1/2/3, CXCL5, and CXCL12) expression in the highly metastatic MDA-MB-231 cell line. The clonogenic survival of BC cells was also reduced by ERA treatment. Strikingly, ERA prevented DMBA-induced tumor growth in Swiss albino mice as depicted by a high animal survival rate (84%) in the ERA group and histopathological analysis. Conclusively, this study revealed that ERA possesses anti-metastatic potential and also reduces the growth of BC in vivo. Moreover, the GC–MS data revealed the presence of biologically active compounds (Lupeol, Phytol, phytosterol) and some rare (9, 19-Cyclolanost) phyto metabolites in ERA extract. However, further studies are suggestive to identify and isolate the therapeutic agents from ERA to combat BC and metastasis.

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All data obtained during this study are included in the manuscript.

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Acknowledgements

We are obliged to the School of Biological Sciences (SBS), PU, and Dr. Muhammad Ali (in charge of animal house) to provide us animal house facility, to conduct in vivo study as well as other basic research facilities. We are thankful to Miss Kokab Farooq for performing the spheroid formation assay as a part of our revised manuscript.

Funding

We are thankful to Higher Education Commission (HEC) Pakistan for funding this research under National Research Program for Universities (NRPU) project (6758/Punjab/NRPU/R&D/HEC/2016).

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Authors and Affiliations

  1. School of Biological Sciences, University of the Punjab, Lahore, 54000, Pakistan

    Sheereen Gull, Asima Tayyeb, Luqman Abid & Naveed Shahzad

  2. Department of Biology, Virtual University of Pakistan, Lahore, Pakistan

    Fareeda Tasneem

  3. Department of Pathobiology, University of Veterinary and Animal Sciences (sub-campus Jhang), Lahore, Pakistan

    Ishtiaq Ahmed

  4. Institute of Microbiology, University of Agriculture, Faisalabad, Pakistan

    Muhammad Aamir Aslam & Muhammad Imran Arshad

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  1. Sheereen Gull
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Contributions

SG contributed to the study design and performed the experiments. FT and IA data interpretation, and manuscript preparation. MAS, AT, LA, MA, and MIA provided research material and performed the statistical analysis. NS Conceptualization, supervision, revising, and editing the paper. All authors read and approved the final manuscript.

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Correspondence to Naveed Shahzad.

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Gull, S., Tasneem, F., Ahmed, I. et al. Ethanolic extract of Euphorbia royleana Boiss. reduces metastasis of breast cancer cells and inhibits tumor progression in vivo. Med Oncol 41, 152 (2024). https://doi.org/10.1007/s12032-024-02378-6

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