Isothiocyanates (ITCs) are a class of natural products with promising anti-cancer activities and chemopreventive prospects. Moringa oleifera is a plant widely cultivated in the tropics and has been popularly used for centuries by locals to treat different diseases. Moringa leaves contain four unique sugar-modified aromatic glucosinolates, which can be converted to moringa isothiocyanates (MICs) by myrosinase also present in the leaves. In this study, we tested the efficacy of MIC-1 on 9 different breast cancer cell lines and found it to be a potent anti-cancer agent against them. Interestingly, the two cells lines most sensitive to MIC-1, BT474 and HCC1954, were both positive for HER2, which is amplified in up to 30% of breast cancer and correlates with poor prognosis. The correlation between HER2 overexpression and hypersensitivity to MIC was further confirmed using pairs of MCF-7 and MDA-MB-231 cells with and without HER2 overexpression. In studies to understand why the HER2+ breast cancer cells were more sensitive to MIC than HER2- lines, we observed higher basal intracellular ROS levels in HER2+ breast cancer cell lines compared to HER2- cells. Moreover, we observed that MIC regulates the abundance of KEAP1 and NRF2 across the different cell lines used in this study. In some cases, MIC-1 upregulated both KEAP1 and NRF2 at the same time, suggesting that it may directly or indirectly inactivate KEAP1 thereby stabilizing NRF2. More efforts are underway to elucidate the precise mechanisms of action. Our work shows that MICs may open new frontiers in breast cancer prevention and therapy, particularly for those with HER2 amplification.

Citation Format: JULIA B. OLAYANJU, Bing Xia. HER2 overexpression induces sensitivity to moringa isothiocyanates in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-017.