In estrogen signaling, nobiletin prevents bone loss due induced by estrogen deficiency in rats (Harada et al., 2011; Matsumoto et al., 2018) and inhibits lower cytotoxicity on MCF-7 estrogen receptor-positive breast cancer cells than on SKBR3 HER2 positive and MDA-MB 468 triple-negative breast cancer cells (Chen et al., 2014). The gene discussed is ESR1; the disease is breast cancer.