In hypoxic breast cancer cells, CUR, EF24, NLE, GEN, RES and RSE resulted in a (i) a complete suppression of IR-induced NFκB-DNA binding activity (ii) attenuation of IR-induced NFκB signal transduction and target transcriptome, (iii) mitigation of IR-induced Akt,, Nos3, Erk1/2, SOD2, p50, p65, TNFα, Birc 1, 2 and 5 and (iv) potentiates IR-induced cell killing, implying that these bioactive phytochemicals may play a key role in regulating NFκB signaling pathway dependent ‘hypoxic processes’ and may potentiate R T in this setting. Here, NOS3 is linked to breast cancer.