Possible Interaction: Tamoxifen and Tretinoin

“Because tamoxifen and all-trans-retinoic acid (ATRA) have additive antitumor effects in preclinical systems, we performed a Phase I/II clinical trial of this combination in patients with advanced breast cancer.”

“ ATRA in the presence of tamoxifen increased NBT reduction and the expression of CD11b in HL-60 cells more effectively than ATRA alone.”

“ ATRA induced the differentiation of APL cell lines NB4 and HT93 and APL cells in primary culture, and this differentiation was also enhanced by tamoxifen.”

“We found that tamoxifen effectively enhanced the differentiation-inducing effect of ATRA.”

“The combination of RA and antiestrogenic compounds, such as tamoxifen , synergistically decreases the proliferation of breast cancer cells and an interplay between retinoid and estrogen signaling has begun to be unraveled, turning these combinations into an appealing strategy for breast cancer treatment.”

“Estradiol increased and anti-estrogens tamoxifen and ICI 164,384) downregulated the expression of both RARalpha and CRABPII proteins in T47D and MCF-7 cells.”

“It was …) that tamoxifen and RU-486 showed a weak inhibitory influence …-47D non-stem cells while all 4 retinoids exerted a significant inhibitory influence on the growth of these non-stem cells, with 4-… < 0.001) at the highest dose, but ineffective (P > 0.05) at the lowest.”

“ResultsIn HER2-overexpressing/ER-positive BT474 cells, combining all-trans retinoic acid (atRA) with tamoxifen or trastuzumab synergistically inhibited cell growth, and altered cell differentiation and cell cycle.”

“Our results showed that the decrease of alpha2beta1 integrin expression by 13-cis RA (10(-5) M, 49.6+/-3.25%) and ATRA (10-… a lesser extent by estradiol, particularly in the case of ATRA at 10(-7) or 10(-9) M. CONCLUSIONS This data suggest that tamoxifen … retinoids ….”

“The lowest fraction of PCNA positive cells was also observed after the simultaneous addition ATRA (10(-5) M) and tamoxifen (10 microM) (30.75%+/-0.95, p<0.01, compared to the tamoxifen group).”

“In addition, the retinoids in combination with TGF-beta1 and tamoxifen (10(-6) M) caused a further reduction in the percentage of proliferating cells.”

“Concentrations of 10 microM TAM and 10 microM ATRA inhibited the proliferation to 63.16 +/- 7.85% and 52.19 +/- 3.21%, respectively.”

“A similar phenomenon was observed when other synthetic retinoids were combined with TMX.”

“Co-treatment of MCF-7 cells over time with RA and TMX resulted in enhanced inhibition of growth.”

“The addition of varying concentrations of retinoic acid (RA) to varying concentrations of tamoxifen (TMX) resulted in an additive effect on the inhibition of proliferation of the ER-positive human carcinoma cell lines (MCF-7).”

“This enhanced inhibition by the combination of retinoids and TMX was also observed with other ER-positive cell lines (ZR-75, T47-D), while no effect was noted on the ER-negative cell lines (MDA-MB-231, Hs578T).”