fenretinide and Burkitt-Lymphoma

Fenretinide (4-HPR) is a synthetic retinoid with cancer chemopreventative potential and clinically manageable side effects, compared to the prototype retinoid, all-trans retinoic acid (RA). 4-HPR has been shown to modulate cell proliferation and induce apoptosis in a variety of human tumor cell types, but its effects on B-cell non-Hodgkin's lymphomas (NHL-B) have not been explored. Treatment of Burkitt's lymphoma Mutu I cells with 3 microM 4-HPR is accompanied by growth arrest, induction of apoptosis, and restricted progression of the cell cycle at the G(1)/S checkpoint. We also observed that 4-HPR elicited a reduced expression of bcl-6 in these cells, which supports the proposed role of bcl-6 as an anti-apoptotic gene. While 4-HPR treatment had no effect on total Rb gene expression, it significantly reduced the state of hyperphosphorylation of Rb, resulting in the predominant existence of Rb in the underphosphorylated state.

Topics: Apoptosis; Blotting, Western; Burkitt Lymphoma; Cell Cycle; Cell Division; DNA-Binding Proteins; Down-Regulation; Fenretinide; Flow Cytometry; G1 Phase; Humans; Phosphorylation; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-6; Retinoblastoma Protein; S Phase; Time Factors; Transcription Factors; Tretinoin; Tumor Cells, Cultured