ABSTRACT
Acute myeloid leukemia (AML) is an aggressive blood cancer. With low survival rates, new drug targets are needed to improve treatment regimens and patient outcomes. Pseudolaric acid B (PAB) is a plant-derived bioactive compound predicted to interact with cluster of differentiation 147 (CD147/BSG). CD147 is a transmembrane glycoprotein overexpressed in various malignancies with suggested roles in regulating cancer cell survival, proliferation, invasion, and apoptosis. However, the detailed function of PAB in AML remains unknown. In this study, AML cell lines and patient-derived cells were used to show that PAB selectively targeted AML (IC50: 1.59 ± 0.47 µM). Moreover, proliferation assays, flow cytometry, and immunoblotting confirmed that PAB targeting of CD147 resulted in AML cell apoptosis. Indeed, the genetic silencing of CD147 significantly suppressed AML cell growth and attenuated PAB activity. Overall, PAB imparts anti-AML activity through transmembrane glycoprotein CD147.
Subject(s)
Apoptosis , Basigin , Cell Proliferation , Diterpenes , Leukemia, Myeloid, Acute , Humans , Basigin/metabolism , Basigin/genetics , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Cell Proliferation/drug effects , Apoptosis/drug effects , Cell Line, Tumor , Diterpenes/pharmacology , Cell Survival/drug effectsABSTRACT
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.
ABSTRACT
Carotenoids are lipid soluble pigments found in various fruits and vegetables and are naturally produced in photoautotrophic plants. Various studies have investigated the properties of carotenoids to determine how they are able to mitigate numerous diseases, including cancer. Carotenoids present in human serum, including ß-carotene, α-carotene, lycopene, ß-cryptoxanthin, zeaxanthin, and lutein have demonstrated the ability to act as anticarcinogenic agents. Prevention of disease is often described to be more effective than treatment; as cancer impacts millions of lives globally, the role of carotenoids in the prevention of oncogenesis for numerous types of cancers have been extensively researched. This review provides an in-depth analysis of the structure and properties of carotenoids, as well as the identified and potential mechanisms by which carotenoids can act as a chemopreventative agent.
