Fig. 5

Tamoxifen sensitizes ER-positive breast cancer to RITA. a Synergy between 4OH-TMX and low dose of compounds in estrogen-positive MCF7 cells. Long-term viability assay (12 days) is shown. b TMX-resistant LCC2 cells (red) are more sensitive to RITA and AF, than MCF7 (WT) cells. Shown is the difference in growth suppression between cell lines treated for 72 h with indicated concentration of compounds (mean ± SD n = 6, *p < 0.05 and ***p < 0.001, one-way ANOVA with Bonferroni’s multiple comparison test). c Pretreatment of 4-OH-TMX (1 μM, 6 days) sensitize the ex vivo cultured breast cancer patient cells from patients #K5, (blue solid dots); #K6 (red dots), and #K10 (black dots) to low dose of RITA (100 nM, treatment for 3 days post-4OH-TMX). Shown is mean ± SD, *p < 0.05, one-way ANOVA with Bonferroni’s multiple comparison test. d Breast cancer patient cells from patients #K7 (black dots), #K8 (blue dots), and #K9 (red dots) that were unresponsive to 4OH-TMX treatment show sensitivity to 100 nM RITA (mean ± SD, **p < 0.01, Student’s t test). e Model illustrating how SULT1A1-dependent compounds can help to overcome TMX resistance. 4OH-TMX-treated relapsed breast tumors display upregulation of SULT1A1, leading to drug resistance. This creates vulnerability to treatment with SULT1A1-dependent RITA, AF, and ONC-1, which eliminate cancer cells by inhibition of TrxR1 and induction of oxidative stress, DNA damage, and apoptosis