The p38 MAPK pathway is critical for 5,5'-dibromodiindolylmethane-induced apoptosis to prevent oral squamous carcinoma cells

European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)
Kyeong-Hee ChoiSung-Dae Cho

Abstract

Cruciferous vegetables contain isothiocyanates including diindolylmethane (DIM) that exhibit cancer chemopreventive effects. We developed a series of synthetic ring-substituted DIM analogs including 5,5'-dibromoDIM that exhibited better inhibitory activity in breast and colon cancer cells than DIM. In this study, we investigated whether 5,5'-dibromoDIM inhibits the proliferation of KB and YD-10B oral squamous carcinoma cell lines. 5,5'-dibromoDIM decreased the cell survival and inhibited the growth of oral cancer cells. Exposure of KB and YD-10B cells to 5,5'-dibromoDIM induced caspase-dependent apoptosis evidenced by poly-ADP ribose polymerase cleavage, accumulation of sub-G1 population, and nuclear condensation and fragmentation. In addition, apoptotic cell death was correlated with damage to the mitochondrial membrane potential through a decrease in the level of Bcl-2 protein expression. Mechanistic studies showed that mitochondria-dependent apoptosis induced by 5,5'-dibromoDIM was mediated by the p38 mitogen-activated protein kinase pathway but not the ERK1/2 and JNK pathway. These results highlight 5,5'-dibromoDIM as an important chemopreventive agent for the clinical treatment of oral cancer through the p38 mitogen-activa...Continue Reading

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Citations

Jan 26, 2016·Chemico-biological Interactions·Vellekkatt JamsheenaSulochana Priya
Jul 19, 2019·International Journal of Molecular Sciences·Chi-Hyun AhnSeong Doo Hong
May 11, 2019·Experimental Cell Research·Daniel W ColeAndrew M Fribley

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