Evaluating the effect of a novel Curcuma amada bioactive, 2,4,6-trihydroxy-3,5-diprenyldihydrochalcone and Avocatin B on mitochondrial metabolism in acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive blood cancer with limited chemotherapy options and negative patient outcomes. Nutraceuticals such as avocatin B, a fatty-acid oxidation (FAO) inhibitor, show promise for treatment. Curcuma amada roots have been used in traditional medicine, but isolated bioactive compounds are rare. 2,4,6-trihydroxy-3,5-diprenyldihydrochalcone (M1) was identified from C. amada as a bioactive molecule. The antileukemic properties of M1 and its effects on mitochondrial metabolism were investigated. M1 reduced the viability of multiple leukemic cell lines but demonstrated toxicity in normal cells. A window of synergy at low concentrations was identified with M1 and avocatin B, which was selective to leukemic cells. The M1 and avocatin B combination inhibited FAO by 60%, a process essential to the synergy. M1 and the combination inhibited complex I of the electron transport chain; M1 also reduces glycolysis. These results demonstrate M1’s potential as a novel chemotherapeutic for AML.