Apoptosis and restriction of G(1)/S cell cycle by fenretinide in Burkitt's lymphoma mutu I cell line accessed with bcl-6 down-regulation.
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.
Hsieh
T
T
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, 10595, USA.
Wu
J M
JM
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D017313:Fenretinide / Q000494:pharmacology*; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6; D016160:Retinoblastoma Protein / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D017313:Fenretinide; D014212:Tretinoin