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• W1998018290 abstract "Fenretinide, 4-(N-hydroxyphenyl) retinamide (4-HPR), has demonstrated anticancer activity associated with a favorable toxicity profile and is now being investigated in several clinical trials. However, its plasma levels in patients have been far lower than the effective concentration required to induce apoptosis (usually 10 microM). This result has led to the synthesis of derivatives with better efficacy. Sodium butyrate's potential as an anticancer agent prompted us to synthesize a butanoate derivative of 4-HPR, 5-hydroxyphenyl butanoate retinamide (5-HPBR) and compare it to the parent compound for antitumor potential in vitro. The cytotoxicity of 5-HPBR was 2- to 6-fold greater than that of 4-HPR against cancer cell lines derived from various tissues. In premalignant bronchial cells (BEAS2B), 5-HPBR exhibited about a 10-fold stronger cytotoxicity than did 4-HPR. Normal CHANG liver cells were unaffected by either 4-HPR or 5-HPBR. Subsequent assays using DNA fragmentation, DAPI staining, FACS and Western blotting suggested that the potent inhibitory effect of 5-HPBR is mediated by apoptosis; the exact mechanism appears to differ among cancer cell types. In transcription assays with COS-1 cells, 5-HPBR selectively activated RARbeta and RARgamma but was a weaker ligand for all 3 subtypes of RAR than either all-trans retinoic acid or 4-HPR. Overall, these data suggest that 4-BHPR may be a promising retinoid with enhanced antitumor activity and reduced toxicity." @default.
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• W1998018290 date "2004-01-01" @default.
• W1998018290 modified "2023-10-16" @default.
• W1998018290 title "Potent effect of 5-HPBR, a butanoate derivative of 4-HPR, on cell growth and apoptosis in cancer cells" @default.
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• W1998018290 doi "https://doi.org/10.1002/ijc.11643" @default.
• W1998018290 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/14735468" @default.
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