Potential Synergistic Effects of the Bioflavonoid Quercetin with the Apoptosis‐Inducer, TRAIL

Abstract

Acute lymphoblastic leukemia (ALL) mutations in lymphocyte precursor cells cause continuous production of lymphocytes. TRAIL, TNF‐related apoptosis‐inducing ligand, stimulates apoptosis in a range of cancer cells. TRAIL is being used more frequently in cancer research because of its directed anti‐cancer abilities, however cancer cells often become resistant to TRAIL treatment. Plant flavonoids such as Kaempferol have been shown to boost the effects of TRAIL and reduce resistance. This study examines the use of both Kaempferol and Quercetin, a plant flavonoid found in several fruits, as co‐treatments with TRAIL in inducing apoptosis in ALL. While the flavonoids have been used in combination with other traditional cancer drugs, little has been done to examine how combinations of flavonoids and molecules like TRAIL affect apoptosis in ALL. We observed an effective concentration for quercetin of 2.5 uM which produced 80% apoptosis in ALL cells. Kaempferol’s effective concentration was 100 uM, resulting in 37% cell death. TRAIL, at concentrations of 50 and 100 nM, showed no effect on Molt‐4 cells, primarily due to Molt‐4’s known resistance to TRAIL. Co‐treatment with quercetin and TRAIL showed suppression of ALL viability as did a triple combination treatment. Co‐treatments also resulted in modification of anti‐ and pro‐apoptotic protein expression. These results indicate that quercetin and other flavonoids may improve the effectiveness of TRAIL, even in TRAIL‐resistant cancer cell lines.