Priming hMSCs with a putative anti-cancer compound, myrtucommulone-a: a way to harness hMSC cytokine expression via modulating PI3K/Akt pathway?
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.
Department of Medical Biology, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey. banu.iskender@yahoo.com.|Betul-Ziya Eren Genome and Stem Cell Center, Erciyes University, 38039, Melikgazi, Kayseri, Turkey. banu.iskender@yahoo.com.
Banu
B
Iskender
Department of Medical Biochemistry, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.|Betul-Ziya Eren Genome and Stem Cell Center, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.
Kenan
K
Izgi
Department of Medical Biology, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.|Betul-Ziya Eren Genome and Stem Cell Center, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.
Cagri
C
Sakalar
Department of Medical Biology, Faculty of Medicine, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.|Betul-Ziya Eren Genome and Stem Cell Center, Erciyes University, 38039, Melikgazi, Kayseri, Turkey.
Halit
H
Canatan
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D059016:Tumor Microenvironment
D000970:Antineoplastic Agents; D016227:Benzoquinones; D017077:Culture Media, Conditioned; D016207:Cytokines; C455139:myrtucommulone A; D010696:Phloroglucinol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C003466:thymoquinone
Conditioned medium; Human mesenchymal stem cells (hMSCs); Myrtucommulone-A; PI3K/Akt pathway; Thymoquinone