Proinflammatory cytokine profile is critical in autocrine GH-triggered curcumin resistance engulf by atiprimod cotreatme
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ORIGINAL ARTICLE
Proinflammatory cytokine profile is critical in autocrine GH-triggered curcumin resistance engulf by atiprimod cotreatment in MCF-7 and MDA-MB-231 breast cancer cells Ajda Coker‑Gurkan1 · Buse Ozakaltun1 · Berre‑Serra Akdeniz1 · Berfin Ergen1 · Pınar Obakan‑Yerlikaya1 · Tunc Akkoc2 · Elif‑Damla Arisan3 Received: 7 April 2020 / Accepted: 16 October 2020 © Springer Nature B.V. 2020
Abstract Active growth hormone (GH) signaling triggers cellular growth and invasion-metastasis in colon, breast, and prostate cancer. Curcumin, an inhibitor of NF-ҡB pathway, is assumed to be a promising anti-carcinogenic agent. Atiprimod is also an antiinflammatory, anti-carcinogenic agent that induces apoptotic cell death in hepatocellular carcinoma, multiple myeloma, and pituitary adenoma. We aimed to demonstrate the potential additional effect of atiprimod on curcumin-induced apoptotic cell death via cytokine expression profiles in MCF-7 and MDA-MB-231 cells with active GH signaling. The effect of curcumin and/or atiprimod on IL-2, IL-4, and IL-17A levels were measured by ELISA assay. MTT cell viability, trypan blue exclusion, and colony formation assays were performed to determine the effect of combined drug exposure on cell viability, growth, and colony formation, respectively. Alteration of the NF-ҡB signaling pathway protein expression profile was determined following curcumin and/or atiprimod exposure by RT-PCR and immunoblotting. Finally, the effect of curcumin with/without atiprimod treatment on Reactive Oxygen Species (ROS) generation and apoptotic cell death was examined by DCFH-DA and Annexin V/PI FACS flow analysis, respectively. Autocrine GH-mediated IL-6, IL-8, IL-10 expressions were downregulated by curcumin treatment. Atiprimod co-treatment increased the inhibitory effect of curcumin on cell viability, proliferation and also increased the curcumin-triggered ROS generation in each GH+ breast cancer cells. Combined drug exposure increased apoptotic cell death through acting on IL-2, IL-4, and IL-17A secretion. Forced GH-triggered curcumin resistance might be overwhelmed by atiprimod and curcumin co-treatment via modulating NF-ҡB-mediated inflammatory cytokine expression in MCF-7 and MDA-MB-231 cells. Keywords Growth hormone · Atiprimod · Curcumin · Proinflammatory cytokine · Apoptosis · Breast cancer Abbreviations DiOC6 3,3′-dihexyloxacarbocyanineiodide DMSO Dimethyl sulfoxide EDTA Ethylenediaminetetraaceticacid Buse Ozakaltun, Berre-Serra Akdeniz, and Berfin Ergen contributed equally * Ajda Coker‑Gurkan [email protected] 1
Science and Letter Faculty, Department of Molecular Biology and Genetics, Istanbul Kültür University, Atakoy Campus, 34156 Istanbul, Turkey
2
Department of Pediatric Allergy‑Immunology, School of Medicine, Marmara University, Istanbul, Turkey
3
Institution of Biotechnology, Gebze Technical University, Gebze, Turkey
ER Estrogen receptor GH Growth hormone HRP Horseradish peroxidase MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide NF-ҡB Nuclear
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