Possible Interaction: Mitoxantrone and Biochanin A

“In accumulation studies, the intracellular level of mitoxantrone was significantly increased in the presence of 2.5 or 25 µM of biochanin A in both murine and human BCRP‐expressing Madin‐Darby canine kidney (MDCK) cells, with no effect in corresponding MDCK/Mock cells.”

“In bi‐directional transport studies, … Papp,B‐A value of mitoxantrone with biochanin A co‐treatment was much lower (6.66±0.84×10−7 cm/s) than that in the absence of biochanin A (21.4±4.14×10−7 cm/s), indicating inhibition of Bcrp1‐mediated efflux.”

“Interestingly, it was found that the intracellular fluorescence of mitoxantrone was decreased 31.9% when co‐incubated with 10 µM biochanin A in P‐glycoprotein (P‐gp) expressing MCF‐7/ADR cells, indicating potential P‐gp stimulation.”

“Surprisingly, the concentrations of mitoxantrone in spleen and kidney were even decreased when biochanin A was co‐administered.”

“Kaempferide, biochanin A , 5,7-dimethoxyflavone, and 8-methylflavone greatly increased the cytotoxicity of mitoxantrone in BCRP-overexpressing breast cancer cells.”

“Chrysin and biochanin A were the most potent BCRP inhibitors, producing significant increases in mitoxantrone accumulation at concentrations of 0.5 or 1.0 microM and in mitoxantrone cytotoxicity at a concentration of 2.5 microM. Flavonoid glycosides had no effects on the BCRP-mediated transport of mitoxantrone.”