IL-32γ enhances TNF-α-induced cell death in colon cancer

• Published in: Molecular carcinogenesis 2014-02, Vol.53 (S1), p.E23-E35
• Main Authors: Park, Eun-Seok, Yoo, Jae-Myung, Yoo, Hwan-Soo, Yoon, Do-Young, Yun, Yeo-Pyo, Hong, JinTae
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Blotting, Western; cell death; Cell Proliferation - drug effects; colon cancer; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; cytokine; Cytokines - metabolism; Enzyme-Linked Immunosorbent Assay; Humans; interleukin-32γ; Interleukins - physiology; Male; Mice; Mice, Inbred BALB C; Mice, Nude; RNA, Small Interfering - genetics; Signal Transduction; TNF-α; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - pharmacology; Xenograft Model Antitumor Assays
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.21990

Interleukin (IL)‐32 is a recently discovered cytokine that appears to play an important role in human colon cancer growth. We investigated that IL‐32γ in combination with TNF‐α remarkably inhibited cell growth of human colon cancer cells (HCT116 and SW620) and tumor growth in xenograft‐bearing nude mice. The transient enforced overexpression of IL‐32γ potentiated the inhibitory effect of TNF‐α on DNA synthesis, cell number and protein content, and enhanced apoptosis in colon cancer cells. We also found that knockdown of IL‐32γ by siRNA showed the abolishment of cell growth inhibitory effect of TNF‐α. The IL‐32γ‐overexpressing colon cancer cells further increased TNF‐α‐mediated expression of p38 MAPK as well as that of Bax, cleaved caspase‐3 and ‐9, but decreased that of antiapoptotic proteins such as Bcl‐2, cellular inhibitor of apoptosis protein (IAP) and X chromosome IAP. In xenograft model, the lipopolysaccharide (LPS)‐injected (1.25 mg/kg) mice inoculated with IL‐32γ‐transfected HCT116 colon cancer cells were more decrease tumor volume and weight than inoculated with vector. Tumor tissues isolated from LPS‐injected mice inoculated with IL‐32γ‐overexpressing colon cancer cells potentiated the expression levels of pro‐apoptotic proteins such as cleaved caspase‐3, 9 and Bax, but decreased that of Bcl‐2. Furthermore, the mice increased IL‐10 production, but decreased IL‐6 levels in serum. In conclusion, our results suggest that IL‐32γ may potentiate TNF‐α‐induced cell growth inhibition through activation of p38 MAPK pathways.