Examining Committee  
Dr. Massimo Marcone, Chair  
Dr. Paul Spagnuolo, Advisor  
Dr. Gisele LaPointe, Advisory Committee Member   
Dr. Praveen Saxena, Department Member  
  
TITLE: 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  
  
ABSTRACT:  
Acute myeloid leukemia (AML) is an aggressive blood cancer with limited effective chemotherapy options and negative patient outcomes. Nutraceuticals such as avocatin B, a fatty-acid oxidation (FAO) inhibitor, are promising options for treatment.  Curcuma amada roots historically have been used in traditional medicine, but isolated bioactive compounds have seldom been studied.  2,4,6-trihydroxy-3,5-diprenyldihydrochalcone (M1) was previously identified from C. amada. This study investigated the antileukemic properties M1 and its effects on mitochondrial metabolism. 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.