Novel Mango Ginger Bioactive (2,4,6-Trihydroxy-3,5-diprenyldihydrochalcone) Inhibits Mitochondrial Metabolism in Combination with Avocatin B.
Varsha JayasankarNikolina VrdoljakAlessia RomaNawaz AhmedMatthew TchengMark D MindenPaul A SpagnuoloPublished in: ACS omega (2022)
Acute myeloid leukemia (AML) is an aggressive blood cancer with limited effective chemotherapy options and negative patient outcomes. Food-derived molecules such as avocatin B (Avo B), a fatty-acid oxidation (FAO) inhibitor, are promising novel therapeutics. The roots of the Curcuma amada plants have been historically used in traditional medicine, but isolated bioactive compounds have seldom been studied. Here, we report that 2,4,6-trihydroxy-3,5-diprenyldihydrochalcone (M1), a bioactive from C. Amada, possesses novel anticancer activity. This in vitro study investigated the antileukemia properties of M1 and its effects on mitochondrial metabolism. In combination with Avo B, M1 synergistically reduced AML cell line viability and patient-derived clonogenic growth with no effect on normal peripheral blood stem cells. Mechanistically, M1 alone inhibited mitochondria complex I, while the M1/Avo B combination inhibited FAO by 60%, a process essential to the synergy. These results identified a novel food-derived bioactive and its potential as a novel chemotherapeutic for AML.
Keyphrases
- acute myeloid leukemia
- stem cells
- peripheral blood
- allogeneic hematopoietic stem cell transplantation
- oxidative stress
- fatty acid
- cell death
- human health
- small molecule
- squamous cell carcinoma
- hydrogen peroxide
- acute lymphoblastic leukemia
- radiation therapy
- mass spectrometry
- reactive oxygen species
- cell therapy
- lymph node metastasis
- electron transfer