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Priming hMSCs with a putative anti-cancer compound, myrtucommulone-a: a way to harness hMSC cytokine expression via modulating PI3K/Akt pathway?

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Tumor Biology

Abstract

Tumour microenvironment is a key factor for cancer growth and metastasis. Tumour surrounding tissue is known to include high number of mesenchymal stem cells which have been thought to have a role in regulating cancer cell behaviour via paracrine signalling. Therefore, modulating human mesenchymal stem cell (hMSC) secretome is highly significant for controlling and treating disease. Since common therapeutic agents are known to enhance cancer resistance, there is a strong urge to define novel agents for developing cell-based therapies. In the present study, we aimed at investigating the effect of active compounds, myrtucommulone-A (MC-A) and thymoquinone (TQ), on hMSC cytokine expression. Our data revealed that MC-A treatment have significantly altered cytokine expression in hMSCs. Upon MC-A treatment, hMSCs decreased the expression levels of various cytokines including TNF-α, VEGF, IL-6, IL-8 and FGF-2. hMSC conditioned medium (CM) primed with MC-A decreased the proliferation, migration ability and clonogenicity of bladder cancer cells and breast cancer cells in comparison to non-primed hMSC medium and hMSC medium primed with TQ. To the best of our knowledge, this study is the first report showing the effects of active compounds, MC-A and TQ, on hMSCs and therefore valuable for highlighting the potential use of active compounds in combination with hMSCs for cell-based targeted cancer therapy.

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Acknowledgments

We are grateful to Prof. Dr. Johann Jauch and Dr. Maël Charpentier (Institut für Organische Chemie der Universität des Saarlandes in Saarbrücken) for providing MC-A. This study was suppoted by the grants from the The Scientific and Technological Research Council of Turkey (No: 115S042, No: 114S542 and No: 113S927).

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Authors and Affiliations

  1. Department of Medical Biology, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey

    Banu Iskender, Cagri Sakalar & Halit Canatan

  2. Department of Medical Biochemistry, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey

    Kenan Izgi

  3. Betul-Ziya Eren Genome and Stem Cell Center, Erciyes University, 38039, Melikgazi, Kayseri, Turkey

    Banu Iskender, Kenan Izgi, Cagri Sakalar & Halit Canatan

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  1. Banu Iskender
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Correspondence to Banu Iskender.

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The effects of conditioned media (hMSC CM, hMSC + MC-A CM, hMSC + TQ CM) on MDA-MB-231 clonogenicity and colony morphology. a Clonogenicity of highly aggressive human breast cancer cell line MDA-MB-231 was impaired upon hMSC + MC-A CM treatment. b The number of colonies formed was not affected from hMSC CM treatment in MDA-MB-231 cells as determined by measurement of the optical density of crystal violet staining. hMSC + TQ CM and hMSC + MC-A CM seemed to reduce clonogenicity of MDA-MB-231 cells. Error bars indicate mean ± SD (n = 2). *p < 0.05 vs MDA-MB-231 control; **p < 0.05 vs MDA-MB-231 control c MDA-MB-231 cells formed dispersed colonies and colony number but not colony morphology was affected from CM treatment. (PDF 8592 kb)

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Iskender, B., Izgi, K., Sakalar, C. et al. Priming hMSCs with a putative anti-cancer compound, myrtucommulone-a: a way to harness hMSC cytokine expression via modulating PI3K/Akt pathway?. Tumor Biol. 37, 1967–1981 (2016). https://doi.org/10.1007/s13277-015-3995-9

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  • DOI: https://doi.org/10.1007/s13277-015-3995-9

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