curcumin and Sarcoma--Ewing

Curcumin is a naturally occurring polyphenolic compound found in the turmeric, which is used as food additive in Indian cooking and as a therapeutic agent in traditional Indian medicine. Curcumin is currently under investigation as a chemotherapeutic and chemopreventive agent in adult cancer models at both pre-clinical and clinical levels. In this preliminary study, we show that curcumin is effective in causing cell cycle arrest, inducing apoptosis, and suppressing colony formation in the Ewing sarcoma cell line SK-NEP-1. Curcumin causes upregulation of cleaved caspase 3 and downregulation of phospho-Akt, producing apoptosis in Ewing sarcoma cells at an inhibitory concentration 50% (IC50) of approximately 4 μM. Our findings indicate a need for further evaluation of curcumin in chemotherapy and chemoprevention of Ewing sarcoma.

Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Bone Neoplasms; Cell Cycle; Cell Line, Tumor; Curcumin; Flow Cytometry; Humans; Proto-Oncogene Proteins c-akt; Sarcoma, Ewing

Curcumin has been demonstrated to have antitumor effects including radiosensitization by modulating many molecular targets including p53. Herein, we investigated the radiosensitizing effect of curcumin in p53 mutant Ewing's sarcoma (ES) cells.. Cells exposed to radiation with or without curcumin were examined for transcriptional and translational levels of p53 downstream targets and its influence in regulated apoptosis, DNA fragmentation, cell survival and clonal expansion.. Curcumin significantly caused radiation induced expression of p21 and Bax, and reduced BclXl, Mcl1 with only marginal Bcl2 modulation. As a positive control to the study, both transcriptional and translational levels of p53 remained unchanged after radiation with/without curcumin. Conversely, curcumin caused radiation-induced apoptosis and DNA fragmentation. Consistently, curcumin enhanced radiation-induced cytotoxicity and clonal expansion.. These results suggest that curcumin potentially radiosensitizes p53-mutant ES cells by regulating IR-modulated p53-response genes. However, the curcumin-associated p53-independent regulation of downstream targets remains to be explored.

Topics: Apoptosis; bcl-2-Associated X Protein; Combined Modality Therapy; Curcumin; Genes, p53; Humans; Infrared Rays; Mutation; Proto-Oncogene Proteins c-bcl-2; Radiation Tolerance; Radiation-Sensitizing Agents; Sarcoma, Ewing; Signal Transduction; Transcription, Genetic