curcumin and Chondrosarcoma

Interleukin (IL)-1 signaling plays an important role in inflammatory processes, but also in malignant processes. The essential downstream event in IL-1 signaling is the activation of nuclear factor (NF)-κB, which leads to the expression of several genes that are involved in cell proliferation, invasion, angiogenesis and metastasis, among them VEGF-A. As microenvironment-derived IL-1β is required for invasion and angiogenesis in malignant tumors, also in chondrosarcomas, we investigated IL-1β-induced signal transduction and VEGF-A expression in C3842 and SW1353 chondrosarcoma cells. We additionally performed in vitro angiogenesis assays and NF-κB-related gene expression analyses. Curcumin is a substance which inhibits IL-1 signaling very early by preventing the recruitment of IL-1 receptor associated kinase (IRAK) to the IL-1 receptor. We demonstrate that IL-1 signaling and VEGF-A expression are blocked by Curcumin in chondrosarcoma cells. We further show that Curcumin blocks IL-1β-induced angiogenesis and NF-κB-related gene expression. We suppose that IL-1 blockade is an additional treatment option in chondrosarcoma, either by Curcumin, its derivatives or other IL-1 blocking agents.

Topics: Cell Line, Tumor; Chondrosarcoma; Curcumin; Gene Expression Regulation; Human Umbilical Vein Endothelial Cells; Humans; Interleukin-1; Interleukin-1 Receptor-Associated Kinases; Neovascularization, Physiologic; NF-kappa B; Phosphorylation; Receptors, Interleukin-1; Signal Transduction; Vascular Endothelial Growth Factor A

Chondrosarcoma is a soft tissue sarcoma with a poor prognosis that is unresponsive to conventional chemotherapy. Surgical treatment leads to severe disability with high rates of local recurrence and life threat. Curcumin, an active compound in turmeric and curry, has been proven to induce tumor apoptosis and inhibit tumor proliferation, invasion, angiogenesis, and metastasis of cancer cells. In this study, we investigated the anticancer effects of curcumin in human chondrosarcoma cells. Curcumin induced apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353) but not in primary chondrocytes. Curcumin induced upregulation of Fas, FasL, and DR5 expression in chondrosarcoma cells. Transfection of cells with Fas, FasL, or DR5 siRNA reduced curcumin-induced cell death. In addition, p53 involved in curcumin-mediated Fas, FasL, and DR5 expression and cell apoptosis in chondrosarcoma cells. Most importantly, animal studies revealed a dramatic 60% reduction in tumor volume after 21 days of treatment. Thus, curcumin may be a novel anticancer agent for the treatment of chondrosarcoma.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Chondrosarcoma; Curcumin; Fas Ligand Protein; fas Receptor; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Receptors, TNF-Related Apoptosis-Inducing Ligand; RNA, Small Interfering; Signal Transduction; Tumor Suppressor Protein p53; Up-Regulation; Xenograft Model Antitumor Assays