Abstract LB-265: Comparison of oleanane triterpenoids and dimethyl fumarate in lung cancer

Lung cancer accounts for the highest number of cancer-related deaths in the United States, highlighting the need for better therapies. Nrf2 is an important therapeutic target as activation of this pathway detoxifies harmful insults and reduces oxidative stress. However, the role of Nrf2 in cancer biology is controversial. Protection against oxidative stress and inflammation can confer a survival advantage to tumor cells, leading to a poor prognosis, and constitutive activation of Nrf2 has been detected in numerous tumors. In our study, we examined the role of two clinically relevant classes of Nrf2 activators, the synthetic triterpenoids (CDDO-Im and CDDO-Me) and dimethyl fumarate (DMF) in mouse macrophages (Raw 264.7) and in VC1 lung cancer cells. Although both triterpenoids and DMF activated Nrf2, CDDO-Im and CDDO-Me were more potent than DMF. Specifically, 25-50 nM CDDO-Im or CDDO-Me increased NQO1 and HO-1 expression 100-fold. Conversely, 10 μM of DMF was necessary to elicit the same effect. Additionally, 100 nM of CDDO-Im significantly (p Citation Format: Ciric To, Darlene B. Royce, Charlotte R. Williams, Renee Risingsong, Michael B. Sporn, Karen T. Liby. Comparison of oleanane triterpenoids and dimethyl fumarate in lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-265. doi:10.1158/1538-7445.AM2015-LB-265