Abstract 2243: Elucidating the mechanism of action of molecular iodine on breast cancer cells

Abstract

Abstract Each year, over 1.7 million women are diagnosed with breast cancer worldwide and about 35% of these diagnosed are expected to die from the disease. A significant barrier to improving treatment of breast cancer lies in our incomplete understanding of breast cancer initiation and metastasis. Regular use of molecular iodine has been shown to reduce the sensitivity of breast cells to the proliferative effects of estrogen, resulting in normalization of breast tissue.The aim of the current study was to evaluate the mechanisms of molecular iodine on two common breast cancer sub-types using well-established breast cancer cell lines. In order to study Luminal A and triple-negative breast cancer in vitro, MCF7 (cells from a luminal A subtype) and MDA-MB231 (cells from a triple-negative subtype), were treated with molecular iodine at various concentrations to measure proliferation and cell death. This was subsequently followed by gene expression analysis of key important molecular markers, which are primarily responsible for cell growth and apoptosis. Primary human mammary epithelial cells derived from healthy female donor were used as an internal control. Data from this study indicated that molecular iodine had potent inhibitory effects on cell growth and showed a dramatic increase in cell death in both breast cancer cell lines. Gene expression analysis using quantitative RT-PCR further confirmed that cell cycle genes controlling G1-S phase transition were largely up-regulated. Changes were not seen in Cyclin B expression levels, which further suggest that cells were arrested before entry into cell division. BCL-2, PPAR-α and PPAR-γ were also up-regulated along with down-regulation of Caspase 3, suggesting molecular iodine induced cell death through activation of a caspase-independent apoptosis pathway. Interestingly, mesenchymal-epithelial transition (MET) occurrence was noticed upon molecular iodine treatment as indicated by sharp increase of GATA3 and E-Cadherin and significant down-regulation of Vimentin in invasive MDA-MB231 cells. Our current study enables us to understand a molecular mechanism controlling tumor cell growth and demonstrates potent cellular effects of molecular iodine on breast cancer cell lines. These results also demonstrate promising effects of molecular iodine for regulation of breast cancer EMT differentiation, which is required for tumor initiation and metastasis. Further studies are underway to determine possible effects of molecular iodine in these breast cancer subtypes using in vitro 3D models. Note: This abstract was not presented at the meeting. Citation Format: Zack Xu, Xin Chen, Noymi Yam, kin Chan, Usha Nagavarapu. Elucidating the mechanism of action of molecular iodine on breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2243. doi:10.1158/1538-7445.AM2017-2243