Possible Interaction: Dexamethasone and Tretinoin

“At 6 months, a significantly … proportion of participants in the all-trans retinoic acid … high-dose dexamethasone group (45 [68%] of 66) than in the high-dose dexamethasone monotherapy group (27 [41%] of …) had a sustained response (OR 3·095, 95% CI 1·516-6·318; p=0·0017).”

“The in vitro inhibitory effect of all-trans retinoic acid (ATRA) on myeloma cell growth may be synergistically potentiated by the activity of dexamethasone (DEX) and alpha-interferon (IFN).”

“When DEX was combined with ATRA , the latter reversed DEX-inhibited ALP activities and osteogenic markers.”

“ResultsLung histology confirmed that DEX treatment inhibited and RA treatment stimulated alveolar formation, whereas concurrent administration of RA with DEX prevented the DEX effects.”

“ConclusionTreatment … Dex in the presence of atRA is able to induce significant amounts of iodide accumulation in breast cancer xenotransplants in vivo due to stimulation of functional NIS protein expression, which opens exciting perspectives for a possible diagnostic and therapeutic role of radioiodine in the treatment of breast cancer.”

“Recently, we have reported stimulation of all-trans retinoic acid (atRA)-induced NIS expression in the human breast cancer cell line MCF-7 by dexamethasone (Dex), resulting in an enhanced therapeutic effect of 131I in vitro.”

“Calpain activity on spectrin was increased by retinoic acid and decreased by dexamethasone (26 ± 14% and -57 ± 5%); retinoic acid mildly but significantly modified the effect of dexamethasone (-44 ± 7%).”

“Cells exhibited a significantly more elongated shape with retinoic acid and a rounder shape with dexamethasone; retinoic acid reversed the effects of dexamethasone.”

“Indeed, retinoic acid and dexamethasone increased (70 ± 7% and 176 ± 5%) cortical actin while retinoic acid suppressed the effect of dexamethasone (90 ± 6%).”

“ Retinoic acid also suppressed the effect of dexamethasone (-21 ± 7%).”

“ Retinoic acid and dexamethasone have a dramatic but mainly opposite effect on actin cytoskeleton remodelling.”

“Furthermore, Dex inhibited all-trans retinoic acid (ATRA) and vitamin D3-induced steroidogenic gene expression and PROG production.”

“Furthermore, in the in vitro clonogenic assay, selective cytotoxicity of 131-I was significantly increased from approximately 17% in MCF-7 cells treated with atRA alone to 80% in MCF-7 cells treated with Dex in the presence of atRA.”

“Furthermore, iodide efflux was modestly decreased after stimulation with Dex in the presence of atRA.”

“The addition of Dex reduced the effective dose of retinoid and prolonged the induction of NIS, especially with AGN190168, suggesting higher efficacy of (131)I after combination treatment.”

“Furthermore, de Ridder et al investigated whether Dex would antagonize the beneficial effects of all-trans RA.”

“Interestingly, the synergistic effect of Dex and RA on differentiation and proliferation of human megakaryoblastic leukemia cell line (HIMeg) has also been reported.”