4-Hydroxyphenylretinamide (4HPR) derivatives regulate aromatase activity and expression in breast cancer cells.
Recent studies exhibit that 4-hydroxyphenylretinamide (4HPR) decreases aromatase activity in breast and placental cells. The effect of synthetic 4HPR analogs on aromatase and expression was examined in three breast cancer cell lines. Most derivatives did not decrease cellular aromatase activity. Two of the analogs even stimulated aromatase activity at the transcriptional level. Only one derivative significantly decreased aromatase in all three breast cancer cell lines and also suppressed CYP19 gene expression in one of the cell line. Placental microsomal aromatase assay rule out the possibility that this compound directly inhibits the aromatase enzyme. A non-genomic mechanism in suppression of cellular aromatase activity of this compound is proposed.
Su
Bin
B
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500W. 12th Avenue, Columbus, OH 43210, USA. Su.112@osu.edu
Mershon
Serena M
SM
Stonerock
Laura A
LA
Curley
Robert W
RW
Brueggemeier
Robert W
RW
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D005260:Female; D017313:Fenretinide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017313:Fenretinide; D001141:Aromatase