Obesity hormones and itaconate mediating inflammation in human colon cancer cells – Another lead to early-onset colon cancer?
Katharina M. Scheurlen,
Dylan L. Snook,
Toriana Alfieri,
Andrew B. Littlefield,
Joan B. George,
Caden Seraphine,
Cheyenne N. Cook,
Andre Rochet,
Jeremy T. Gaskins,
Susan Galandiuk
Affiliations
Katharina M. Scheurlen
Price Institute of Surgical Research, The Hiram C. Polk, Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA
Dylan L. Snook
Price Institute of Surgical Research, The Hiram C. Polk, Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA
Toriana Alfieri
Price Institute of Surgical Research, The Hiram C. Polk, Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA
Andrew B. Littlefield
Price Institute of Surgical Research, The Hiram C. Polk, Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA
Joan B. George
Price Institute of Surgical Research, The Hiram C. Polk, Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA
Caden Seraphine
Price Institute of Surgical Research, The Hiram C. Polk, Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA
Cheyenne N. Cook
Price Institute of Surgical Research, The Hiram C. Polk, Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA
Andre Rochet
Price Institute of Surgical Research, The Hiram C. Polk, Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA
Jeremy T. Gaskins
Department of Bioinformatics & Biostatistics, University of Louisville, 485 E. Gray Street, Louisville, KY, 40202, USA
Susan Galandiuk
Price Institute of Surgical Research, The Hiram C. Polk, Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA; Corresponding author.
Background: Chronic inflammation is a key feature of obesity and a hallmark of colon cancer (CC). The obesity-related hormones leptin and adiponectin alter inflammatory gene profiles in cancer, but their specific role in CC is unclear. We have previously studied the effects of leptin and the macrophage-specific mediator itaconate on M2-like macrophages. This current study evaluates their effects on CC cells. Methods: HT-29 CC cells (derived from a young patient, stage III CC) were treated with either leptin, adiponectin, 4-octyl itaconate (OI) or dimethyl itaconate (DI). Gene expression after treatment was analyzed at four time points (3, 6, 18, and 24 h). Results: CCL22 was upregulated after treatment with adiponectin (at 18 h [FC 16.3, p < 0.001]). IL-8 expression increased following both adiponectin (at 3 h [FC 68.1, p < 0.001]) and leptin treatments (at 6 h [FC 7.3, p < 0.001]), while OI induced downregulation of IL-8 (at 24 h [FC −5.0, p < 0.001]). CXCL10 was upregulated after adiponectin treatment (at 6 h [FC 3.0, p = 0.025]) and downregulated by both OI and DI at 24 h, respectively (OI [FC −10.0, p < 0.001]; DI [FC −10.0, p < 0.001]). IL-1β was upregulated after adiponectin treatment (at 3 h [FC 10.6, p < 0.001]) and downregulated by DI (at 24 h [FC −5.0, p < 0.001]). TNF-α expression was induced following adiponectin (at 6 h [FC 110.7, p < 0.001]), leptin (at 18 h [FC 5.8, p = 0.027]) and OI (at 3 h [FC 91.1, p = 0.001]). PPARγ was affected by both OI (at 3 h [FC 10.1, p = 0.031], at 24 h [FC −10.0, p = 0.031]) and DI (at 18 h [FC −1.7, p = 0.033]). Conclusions: Obesity hormones directly affect inflammatory gene expression in HT29 CC cells, potentially enhancing cancer progression. Itaconate affects the prognostic marker PPARγ in HT29 CC cells. Leptin, adiponectin and itaconate may represent a link between obesity and CC.
