Possible Interaction: Tretinoin and Valproic Acid

“Valproic acid VPA ) inhibits histone deacetylase activity and, synergizing with all‐trans retinoic acid (ATRA), achieves differentiation induction of myeloid blast cells in vitro.”

“If patients relapse after an initial response to VPA, ATRA has the potential to induce a prolonged second response.”

“ Valproic acid (VPA) has been shown to inhibit histone deacetylase activity and to synergize with all-trans retinoic acid (ATRA) in the differentiation induction of acute myelogenous leukemia (AML) blasts in vitro.”

“Additive antitumour effects were produced in tumour xenografts by combining VPA with ATRA treatment.”

“In view of these findings, we evaluated the antitumor effects induced by combined VPA and ATRA treatment in a xenograft model implanted with poorly differentiated human squamous cell carcinoma.”

“Here we show, using KG-1 and MV4-11 AML cells and recombinant 293 cells, that the histone deacetylase (HDAC) inhibitors trichostatin A (TSA), valproic acid (VPA), and FK228 potentiated ATRA induction of FR-beta gene transcription and FR-beta mRNA/protein expression.”

“In addition to the synergistic effect of ATRA plus VPA on HL-60 cells, the optimal concentration of 1 mM VPA plus 0.5 µM ATRA increased the cytotoxic sensitivity of HL-60 cells to NK cells.”

“In conclusion, the combination of VPA and ATRA not only induced the differentiation of HL-60 cells, but also induced enhancement of the sensitivity of HL-60 cells to NK cells by downregulating the expression of HLA-ABC and upregulating the expression of CD54, but not MICA/MICB.”

“Cytarabine (0.01-0.05 μM) showed a dose-dependent antiproliferative effect on AML cells, and in contrast … reached statistical significance even at 0.01 μM.ConclusionsEven low levels of cytarabine, and especially when combined with ATRA … valproic acid , can decrease T cell viability, … and decrease the cytokine release.”

“Our data demonstrated that valproic acid can act in concert with retinoic acid to enhance the commitment of stem cells into the skeletal myocyte lineage reinforcing the notion that histone acetylation is important for skeletal myogenesis.”

“A significant cell growth inhibition was observed after the treatment with VPA , which was further strengthened by the addition of ATRA.”

“Here, we show that VPA combined with ATRA led to hyperacetylation of histone H3 and a significant alteration of gene expression in cervical cancer cells, including RARβ2 gene expression, which was upregulated 50- to 90-fold.”

“Therefore, we hypothesized that the combination of VPA and ATRA could restore RARβ2 expression, thus resulting in enhanced anti-neoplastic activity in cervical cancer.”