Signaling Pathways of All-Trans Retinoic Acid (ATRA)-Induced Apoptosis in Mantle Cell Lymphoma (MCL) (original) (raw)

Blood, 2007

Abstract

MCL, characterized by the t(11;14), results in the overexpression of cyclin D1, and typically has an aggressive clinical course. The disease is not curable by conventional therapy, and new modalities are needed. A MCL cell line, Granta, has been studied and has a complex karyotype and genetic alterations of cell cycle regulatory genes. ATRA is a metabolic derivative of retinoic acid (RA). Upon binding with ATRA, its receptors become transcriptionally activated and transactivate their target genes leading to cell growth arrest or apoptosis. We hypothesized that ATRA would lead to apoptosis or cell growth arrest in Granta MCL cells. We used ATRA nanodisks for increased solubilization and in vivo delivery. Reactive oxygen species (ROS) were measured with fluorescence-activated cell sorting (FACS) following incubation at 6 hours (h) and 24 h with ATRA (12.5–50nM). At 6 h, ATRA induced dose-dependent generation of ROS, which returned to baseline at 24 h. The levels of ROS in untreated co...

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