Possible Interaction: Tretinoin and Histone Deacetylase Inhibitors

“Pre-clinical evidence suggests histone deacetylase inhibitors enhance retinoic acid signaling in a variety of solid tumors.”

“Restored retinoid sensitivity was observed in combining retinoid with a histone deacetylase inhibitor significantly inhibited cell growth in vitro, suppressed subcutaneously transplanted tumor growth, and prolonged survival of tumor-bearing mice in vivo by more strongly inducing apoptosis and p21 expression in CTCL cells than either agent alone.”

“We found … of four HDIs (CI-994, MS-… TSA) with retinoids all-trans-retinoic acid (ATRA) or 13-cis-retinoic acid (13-CRA) or our atypical retinoic acid metabolism blocking agents (RAMBAs) …-1) or 2 (VN/66-1) produced synergistic anti-neoplastic activity on human LNCaP prostate cancer cells.”

“Conclusions: The combination of ATRA and the histone deacetylase inhibitor TSA elicits an additive inhibition of cell proliferation in RCC cell lines.”

“Other agents such as histone deacetylase inhibitors may significantly increase retinoid activity in a number of malignant cell types.”

“ HDAC-inhibitors may enhance the activity of RA on RA-responsive melanoma cells.”

“In cells from PLZF-RAR alpha/RAR alpha-PLZF transgenic mice and cells harboring t(15;17), HDACIs induced apoptosis and dramatic growth inhibition, effects that could be potentiated by RA.”

“Treatment of APLs with RA, and of other AMLs with RA plus HDAC inhibitors (HDACi), results in myeloid differentiation.”

“On the other hand, histone deacetylase inhibitors , such as cholesteryl butyrate, present differentiating activity and.can potentiate action of drugs such as all-trans retinoic acid.”

“Objectives: All-trans retinoic acid (ATRA) is one of the most successful examples of differentiation agents and histone deacetylase inhibitors , such as tributyrin (TB), are known for their antitumor activity and potentiating action of drugs, such as ATRA.”