Magnolol and Honokiol Inhibited the Function and Expression of BCRP with Mechanism Exploration

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 23; p. 7390
• Main Authors: Yu, Chung-Ping, Li, Pei-Ying, Chen, Szu-Yu, Lin, Shiuan-Pey, Hou, Yu-Chi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.12.2021; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; ABC transporters; Angiogenesis; Animals; Apoptosis; ATP Binding Cassette Transporter, Subfamily G, Member 2 - metabolism; BCRP; Biphenyl Compounds - metabolism; Biphenyl Compounds - pharmacology; Breast cancer; Cancer therapies; Cell Survival - drug effects; Chemotherapy; Dogs; Drug Resistance, Multiple - drug effects; Drug Resistance, Neoplasm - drug effects; Drugs; EGFR; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - metabolism; Growth factors; honokiol; Investigations; Lignans - metabolism; Lignans - pharmacology; Madin Darby Canine Kidney Cells; Magnolia - chemistry; magnolol; MDR; Multidrug resistance; Neoplasm Proteins - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Phosphorylation - drug effects; Plant Extracts - metabolism; Plant Extracts - pharmacology; Polyphenols; Polyphenols - metabolism; Polyphenols - pharmacology; Proteins; Signal transduction; Signal Transduction - drug effects; Substrates; United States > US; BCRP; honokiol; MDR; magnolol; EGFR
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26237390

Breast cancer resistance protein (BCRP), one of the ATP-binding cassette (ABC) transporters, was associated with the multidrug resistance (MDR) of chemotherapy. Magnolol (MN) and honokiol (HK) are major bioactive polyphenols of . This study investigated the effects of MN and HK on the function and expression of BCRP for the purpose of developing BCRP inhibitor to overcome MDR. Cell lines including MDCKII-BCRP and MDCKII-WT were used for evaluating the function and expression of BCRP. The results showed that MN (100-12.5 µM) and HK (100-12.5 µM) significantly decreased the function of BCRP by 80~12% and 67~14%, respectively. In addition, MN and HK were verified as substrates of BCRP. Furthermore, MN and HK reduced the protein expression of BCRP, and inhibited the phosphorylation of epidermal growth factor receptor (EGFR) and phosphatidylinositol 3-kinase (PI3K). In conclusion, both MN and HK decreased the function and expression of BCRP via EGFR/PI3K signaling pathway. Therefore, both compounds were promising candidates for reversing the MDR of chemotherapy.