Berberine Activates Aryl Hydrocarbon Receptor but Suppresses CYP1A1 Induction through miR-21-3p Stimulation in MCF-7 Breast Cancer Cells

• Published in: Molecules (Basel, Switzerland) Switzerland), 2017-10, Vol.22 (11), p.1847
• Main Authors: Lo, Sheng-Nan, Wang, Chun-Wei, Chen, Yueh-Shieh, Huang, Chiung-Chiao, Wu, Tian-Shung, Li, Lih-Ann, Lee, I-Jung, Ueng, Yune-Fang
• Format: Article
• Language: English
• Subjects: Activation; Aromatic compounds; aryl hydrocarbon receptor; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Berberine; Berberine - analogs & derivatives; Berberine - chemistry; Berberine - pharmacology; Berberine Alkaloids - chemistry; Berberine Alkaloids - pharmacology; Breast cancer; breast cancer cells; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; CYP1A1; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP1A1 - metabolism; Cytochrome P450; Cytotoxicity; Dose-Response Relationship, Drug; Estrogen receptors; Estrogens; Female; Gene Expression Regulation, Neoplastic - drug effects; Humans; Hydrocarbons; Immunomodulation; MCF-7 Cells; MicroRNAs - genetics; miR-21-3p; Molecular Structure; mRNA stability; Proteins; Receptors, Aryl Hydrocarbon - genetics; Receptors, Aryl Hydrocarbon - metabolism; Ring opening; Statistical analysis; Transfection
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22111847

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.