Natural isothiocyanates may aid in metastasis control by down-regulation of HIF-1α in breast cancer cells

9^th Indo Global Summit on Cancer Therapy

November 02-04, 2015 Hyderabad, India

Madhumita Roy, Ruma Sarkar, Sutapa Mukherjee and Jaydip Biswas

Chittaranjan National Cancer Institute, India

Posters-Accepted Abstracts: J Cancer Sci Ther

Abstract :

Secondary breast cancer occurs when cancer cells spread from the primary tumor to some distant parts through the lymphatic or blood system. Hypoxia-inducible factor 1�± (HIF-1�±) plays a crucial role in facilitating tumor progression and metastasis. Hence reducing the levels of HIF-1�± might be an important anticancer strategy. It is therefore important to understand the key cellular events involved in HIF-1�± activation. Exploration of natural compounds having little or no toxicity in this regard is very important. Phenethyl isothiocyanate (PEITC), a natural isothiocyanate, found in cruciferous vegetables is stud with anticancer properties. Effect of PEITC on the expression of HIF-1�± and HSP90 in breast adenocarcinoma cell lines (MCF-7 and MDA-MB-231) under both normoxia and hypoxia had been explored. ROS plays an important role in up-regulation of HIF-1�± and HSP90. PEITC induced nuclear accumulation of Nrf2, increased the activities of several antioxidant enzymes and thus reduced the ROS burden of the tumor cells by acting as an indirect antioxidant. This resulted in the down-regulation of HSP90 and thereby HIF-1�± expression. HSP90 was also found to be involved in the regulation of HIF-1�±. A probable link between down-regulation of HIF-1�± with reduction of ROS by PEITC through induction of Nrf2 was determined. PEITC, by virtue of its modulatory effect on HIF-1�± could aid in control of metastasis by altering two important metastatic proteins MMP 2 & 9 and VEGF. These series of events culminated in retardation of adhesion, aggregation, migration and invasion of the breast cancer cells.

Biography :

Email: mitacnci@yahoo.co.in