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Glitazone loaded fat enhances adiponectin production and inhibits breast cancer cell proliferation

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Abstract

Obesity and diabetes are both associated risk factors for developing breast cancer and poor patient outcomes. Adipose cells are an important endocrine system and are the main producer of adiponectin, with lean patients having higher circulating levels. Patients with diabetes are often treated with thiazolidinediones, glitazones, which also increase adiponectin production. Importantly high circulating levels of adiponectin and treatment with glitazone are associated with increased breast cancer patient survival. This study investigates the potential of using adipose tissue laden with glitazones to act as a drug depot, increase adiponectin levels, and locally release glitazones to inhibit breast cancer cell proliferation. The breast cancer cell lines MCF-7 and MBA-MD-231, and the normal breast epithelial cell line MCF-10A were exposed to media containing a range of concentrations of recombinant adiponectin, pioglitazone, or conditioned media obtained from pioglitazone laden adipose tissue to determine the impact of the different treatments on cell proliferation. The MCF-7 cells demonstrated the greatest reduction in proliferation upon exposure to adiponectin and pioglitazone with lower reductions observed in the MDA-MD-231 and MCF-10a cell lines. All three cell lines exhibited reductions in proliferation in the presence of pioglitazone loaded adipose tissue. Additionally, adiponectin and pioglitazone levels were higher in the media from glitazone loaded adipose tissue. Drug loaded adipose tissue could potentially be used to deliver adiponectin and glitazone to breast cancer cells and inhibit proliferation. Future research will examine the potential efficacy of this treatment approach in vivo.

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Acknowledgements

This work is funded by the NIH Award Number 1 R21 CA187829-01. The authors would like to thank the Department of Surgery Research Laboratory and the Preclinical Research Resource at Huntsman Cancer Institute for their assistance in this work.

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  1. Department of Surgery, University of Utah, Salt Lake City, UT, 84132, USA

    Jill Shea, Kyle Edwards & Jayant Agarwal

  2. Department of Internal Medicine, University of Utah, Salt Lake City, UT, 84132, USA

    Christi Terry

  3. University of Utah Surgery, 30 N 1900 E, 3b400, Salt Lake City, UT, 84112-9057, USA

    Jayant Agarwal

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Shea, J., Terry, C., Edwards, K. et al. Glitazone loaded fat enhances adiponectin production and inhibits breast cancer cell proliferation. Mol Biol Rep 46, 6485–6494 (2019). https://doi.org/10.1007/s11033-019-05094-x

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