Abstract
Berberine and the methylenedioxy ring-opening derivatives palmatine and jatrorrhizine are active ingredients in immunomodulatory plants, such as goldenseal. This study aimed to illustrate the effects of protoberberines on aryl hydrocarbon receptor (AhR) activation and cytochrome P450 (CYP) 1 in the estrogen receptor (ER)α(+) MCF-7 breast cancer cells. Among protoberberines at non-cytotoxic concentrations (≤10 μM), berberine had the most potent and statistically significant effects on AhR activation and CYP1A1/1A2/1B1 mRNA induction. The 24-h exposure to 10 μM berberine did not change CYP1A1 mRNA stability, protein level and function. Berberine significantly increased micro RNA (miR)-21-3p by 36% and the transfection of an inhibitor of miR-21-3p restored the induction of CYP1A1 protein with a 50% increase. These findings demonstrate that the ring opening of the methylenedioxyl moiety in berberine decreased AhR activation in MCF-7 cells. While CYP1A1 mRNA was elevated, berberine-induced miR-21-3p suppressed the increase of functional CYP1A1 protein expression.
Highlights
The aryl hydrocarbon receptor (AhR) downstream targets, cytochrome P450 (CYP) 1 isoforms, play very important roles in the detoxification and bioactivation of environmental pollutants, carcinogens and physiological compounds, such as benzo(a)pyrene (B(a)P) and estradiol (E2) [1]
dioxin-responsive element (DRE) Activation by Berberine, Palmatine and Jatrorrhizine In MCF-7 cells, cell growth was significantly suppressed after 24-h exposure to cisplatin and In MCF-7 cells, cell growth was significantly suppressed after 24-h exposure to cisplatin and doxorubicin at concentrations greater than 10 and 0.2 μM, respectively (Figure S1)
Results of Polymerase Chain Reaction (PCR) analysis consistently demonstrated that berberine caused the most-potent analysis consistently demonstrated that berberine caused the most-potent induction of CYP1A1 mRNA
Summary
The aryl hydrocarbon receptor (AhR) downstream targets, cytochrome P450 (CYP) 1 isoforms, play very important roles in the detoxification and bioactivation of environmental pollutants, carcinogens and physiological compounds, such as benzo(a)pyrene (B(a)P) and estradiol (E2) [1]. CYP1A1 and CYP1B1 are predominantly expressed in extrahepatic tissues including the breasts (mammaries) [3]. CYP1A2 is predominantly a hepatic isoform, CYP1A2 protein has been identified in breast cancer tissues [4]. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and B(a)P induced CYP1 through the binding. The AhR nuclear translocator (ARNT) carries the AhR–ligand complex to interact through the binding of the AhR [5].ofThe nuclearCYP1A2 translocator. AhR– in with CYP1 the dioxin-responsive element (DRE) theAhR. CYP1B1carries genes,the resulting ligand complex to interact with the dioxin-responsive element of the CYP1A1, CYP1A2 and transcriptional induction. Compared to the dramatic increase in CYP1A1 mRNA by TCDD in estrogen
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