Abstract 1458: Hyperthermia and radiotherapy in combination with curcumin prevent tumor cell migration and progression of breast cancer

Abstract

Abstract We have demonstrated that hyperthermia (HT)-induced nitric oxide regulates NF-kB, and that potentiates radiotherapy (RT)-induced breast cancer cell death. As a follow-up, in this study we investigated the efficacy of pharmacologically-safe bioactive curcumin (CUR) in combination with HT and therapeutic doses of radiation in regulating breast cancer progression. Human breast adenocarcinoma (MCF-7) cells were either mock-irradiated, exposed to 2Gy (IR), exposed to HT (43oC for 1 h) and /or treated with CUR in the presence or absence of radiation exposure. The treated/irradiated cells were examined for (i) transcriptional modulations of ninety three molecules that are directly involved in tumor invasion and metastasis; (ii) cellular localization of cMYC, p65, p53, MMP2 and MMP9; (iii) cellular migration; (iv) metabolic activity and (v) cell death. Compared to mock-IR control, QPCR profiling demonstrated a significant modulation of tumor invasion and metastasis molecules in IR exposed cells. Conversely, combinations like ‘HT with IR’, ‘CUR with IR’ or ‘CUR with HT’ robustly inhibited IR-induced and in parallel conferred IR suppressed tumor invasion and metastasis molecules in this setting. More importantly, CUR combined with both HT and IR significantly inhibited (through blocking seventy four genes) tumor invasion and metastasis molecules. Scratch wound assay demonstrated complete inhibition of tumor cell migration in CUR-HT-IR exposed cells as opposed to every stand alone and combinations investigated. Likewise, cytotoxic assay, MTT showed a significant cell killing with CUR-HT-IR exposure compared to all other groups. Furthermore, we observed significant and robust apoptotic characteristics in CUR-HT-IR exposed cells. These data together with our earlier report clearly demonstrate that CUR in combination with HT and IR may significantly inhibit breast cancer progression through combinatorial regulation of tumor invasion and metastasis molecules. The findings further imply that CUR may significantly enhance the IR dose reduction factor at least for the treatment of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1458. doi:1538-7445.AM2012-1458