Promising natural products against glucocorticoid resistant acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is one of the most common pediatric cancers in developed countries. Although, ALL has a high cure rate (> 94%), up to a quarter of patients relapse and at that stage their prognosis is poor. Refractory ALL cases are commonly associated with drug resistance, particularly to glucocorticoid (GC) treatment, an integral component of the therapy. Our main objective is to identify new compound leads from terrestrial natural products to serve as tool compounds and potential therapeutic agents. To evaluate hundreds of natural product fractions, we developed dexamethasone (Dex) pre-B resistant ALL stable cell lines. These Dex resistant cells were characterized via microarray gene expression and protein analysis to interrogate the glucocorticoid pathway. Using CellTiter Glow proliferation assay, we screened our natural product fractions against Dex resistant cell lines and PBMCs. Promising compound leads have been identified and we are current validating them. Our preliminary mechanistic studies on mode of action have focused on the jatrophone sesquiterpenoids and tripterine derivatives. These compound leads will provide insights into GC resistant ALL.