Diacerein attenuates 1,2‐dimethylhydrazine induced colon cancer progression in rats: Modulation of IL‐6/STAT3/ lncRNA HOTAIR pathway

Abstract

Diacerein (DIA) is an FDA approved anti‐inflammatory drug. Over the past few years, several studies reported its anti‐proliferative action against different types of cancers. However, the anti‐tumor effect against colon cancer remains obscure. Colon cancer is one of the top solid tumors diagnosed around the world. The current study aims to investigate DIA‐associated anti‐tumor effect In vivo and invitro and to further elaborate the potential underling molecular mechanism. In vitro, human Caco‐2 colon cancer cell lines were treated with serial dilution of DIA and were evaluated for cell viability and apoptotic percentages via MTT and Annexin V assays, respectively. In vivo, subcutaneous injection of 1,2‐dimethylhydrazine (DMH) (20 mg/kg for 15 weeks) was used to induce colon carcinogenesis. DIA oral administration at dose of 50 mg/kg/day for additional of 8 weeks was tested. This therapeutic regimen showed significant anti‐tumor effect and improvement of colonic tissue structure as evident by histopathological examination. Mechanistically, colon tissue samples were collected for ELISA and immunohistochemical analyses. Data showed that DIA treatment reduced colonic inflammatory status as evident by reduction of TLR4, NF‐κB and TNF‐α protein levels. In addition, DIA treatment reduced angiogenesis levels as evident by downregulation of VEGF tissue expression levels. Furthermore, DIA treatment modulated Wnt/β‐catenin pathway, induced caspase‐3 expression and interrupted IL‐6/STAT3/lncRNA HOTAIR axis. Altogether, this study provides evidence that DIA treatment might be beneficial in controlling colon cancer progression via multi pathways targeting mechanism.