4-Hydroxyphenylretinamide (4HPR) derivatives regulate aromatase activity and expression in breast cancer cells

Abstract

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.

Knockdown of NR3C1 inhibits the proliferation and migration of clear cell renal cell carcinoma through activating endoplasmic reticulum stress–mitophagy

“…The simultaneous activation of both pathways reflects the severity of mitophagy. Numerous studies have demonstrated that excessive activation of mitophagy can lead to the death of various tumor cells [ 34 – 36 ]. PINK1 can inhibit the growth of several tumors by activating mitophagy [ 37 , 38 ].…”

Retinol inhibits aromatase activity and expression in vitro

“…We [31] and others [32,33] previously demonstrated that the synthetic retinoid 4-hydroxyphenylretinamide (4-HPR) inhibits the activity of aromatase in vitro. However, despite the established chemopreventive effect of retinoids towards breast cancer, and the crucial role of aromatase in the growth of estrogen-dependent tumors, the effects of ROH and other naturally occurring retinoids on aromatase activity have not, to the best of our knowledge, been investigated.…”

“…The model systems used in this study, JEG-3 human placental cells used as a source of microsomal aromatase and the estrogen-receptorpositive MCF-7 human mammary cancer cell line, have been used extensively in aromatase research [30][31][32][33]37,38] and thus are appropriate in vitro models. Plasma concentrations of ROH reach 2-3 μM in humans [2,39].…”

Συμβολή στον χαρακτηρισμό και στη διερεύνηση βιολογικών ιδιοτήτων των στύλων ειδών γένους crocus

“…Μικρότερη τοξικότητα από το ρετινοϊκό οξύ με πιθανά ευεργετικά αποτελέσματα σε καρκινικά κύτταρα μαστού έχει εμφανίσει και το ανάλογο 4HPR σε πειράματα που έγιναν σε τρωκτικά [Costa et al 1994;Su et al 2008]. In vivo πειράματα σε αρουραίο έδειξαν ότι το 4HPR συσσωρεύεται επιλεκτικά στους ιστούς του μαστού και αναστέλλει την καρκινογένεση [Simeone and Tari 2004] ενώ πρόσφατα δείχθηκε μείωση του κινδύνου ανάπτυξης για δεύτερο καρκίνο του μαστού [Decensi et al 2007] και επαγωγή του φαινομένου της αυτοφαγίας (η διατήρηση κάποιου οργανισμού στη ζωή με θρεπτικές ουσίες που προέρχονται από το ίδιο του το σώμα) [Fazi et al 2008].…”