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Crocin and Metformin suppress metastatic breast cancer progression via VEGF and MMP9 downregulations: in vitro and in vivo studies

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Abstract

Metastatic breast cancer remains a serious health concern and numerous investigations recommended medicinal plants as a complementary therapy. Crocin is one of the known anticancer bio-component. Recently, the inhibitory effect of metformin has been studied on the various aspects of cancer. However, no study reported their combination effects on metastatic breast cancer. In the present study, we have assessed their anti-metastatic effects on in vitro and in vivo breast cancer models. Using MTT assay, scratch, and adhesion tests, we have evaluated the cytotoxic, anti-invasive and anti-adhesion effects of crocin and metformin on 4T1 cell line, respectively. Their protective effects and MMP9 as well as VEGF protein expression levels (Western blotting) investigated in the 4T1 murine breast cancer model. Our results showed that both crocin and metformin reduced cell viability, delayed scratch healing and inhibited the cell adhesion, in vitro. While crocin alone restored the mice’s weight reduction, crocin, metformin, and their combination significantly reduced the tumor volume size and enhanced animal survival rate in murine breast cancer model, responses that were associated with VEGF and MMP9 down-regulation. These findings suggest that a combination of crocin and metformin could serve as a novel therapeutic approach to enhance the effectiveness of metastatic breast cancer therapy.

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All data generated or analyzed during this study are included in this published article. Additional information is available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank the laboratory in Birjand University of Medical Sciences.

Funding

This study was made possible by a Grant (ir.bums.REC.1396.268) from the Birjand University of Medical Sciences.

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Authors and Affiliations

  1. Student Research Committee and Department of Molecular Medicine, Birjand University of Medical Sciences, Birjand, Iran

    Ali Farahi & Hossein Javdani

  2. Cellular and Molecular Research Center, Birjand University of Medical Sciences, P.O. Box 9717853577, Birjand, Iran

    Ali Farahi, Mohammad Reza Abedini, Hossein Javdani, Elham Chamani & Reyhane Hoshyar

  3. Department of Cellular and Molecular Medicine, University of Ottawa School of Medicine, Ottawa, ON, Canada

    Mohammad Reza Abedini

  4. Department of Microbiology, Shahr-e-Qods Branch, Islamic Azad University, Tehran, Iran

    Laleh Arzi

  5. Department of Viral Vaccine Production, Pasteur Institute of Iran, Research and Production Complex, Karaj, Iran

    Ramin Farhoudi

  6. Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI, USA

    Nazanin Talebloo

  7. Department of Chemistry, College of Natural Science, Michigan State University, East Lansing, MI, USA

    Nazanin Talebloo

  8. Microbiology and Molecular Genetics Department, Michigan State University, East Lansing, MI, 48824, USA

    Reyhane Hoshyar

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  1. Ali Farahi
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  2. Mohammad Reza Abedini
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  3. Hossein Javdani
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Correspondence to Mohammad Reza Abedini or Reyhane Hoshyar.

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This study was made possible by ethical code (ir.bums.REC.1396.268) from the Birjand University of Medical Sciences.

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Farahi, A., Abedini, M.R., Javdani, H. et al. Crocin and Metformin suppress metastatic breast cancer progression via VEGF and MMP9 downregulations: in vitro and in vivo studies. Mol Cell Biochem 476, 3341–3351 (2021). https://doi.org/10.1007/s11010-020-04043-8

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