Possible Interaction: Daunorubicin and Genistein

“ Genistein acts synergistically with drugs such as tamoxifen, cisplatin, 1,3-bis 2-chloroethyl-1-nitrosourea (BCNU), dexamethasone, daunorubicin and tiazofurin, and with bioflavonoid food supplements such as quercetin, green-tea catechins and black-tea thearubigins.”

“However, we found that exposure to 200 microM genistein elicited an elevation in intracellular accumulation of rhodamine 123 (R123) and daunorubicin (DNR) in Pgp-expressing cell lines.”

“Biochanin-A, genistein , quercetin, chalcone, silymarin, phloretin, morin, and kaempferol, at 100 microM concentrations, all significantly increased the accumulation of both DNM and VBL in Panc-1 cells, with morin increasing DNM and VBL accumulation by 546 +/- 50% (mean +/- SE, n = 9) and 553 +/- 37% (n = 9), respectively.”

“In the majority of samples PSC 833 (19/26), CsA (22/26) and Vp (15/18) sensitized the cells to DNR whereas genistein made 25 out of 26 samples more resistant to DNR.”

“Thus, although the combination of DNR with genistein appeared to be as sensitive as the combination of calcein-AM with VCR, the former may be used to probe specific MRP activity whereas the latter provides a combined (P-gp + MRP) functional MDR parameter.”

“ Genistein , verapamil, cyclosporin A and oua‐bain were also each able to modify, to some extent, accumulation of daunorubicin , whilst having essentially no effect on calcein accumulation.”

“The active transport of DNR in GLC4/ADR cells appeared to be a saturable process with an apparent Km of DNR of 1.4 +/- 0.4 microM. Genistein increased the apparent Km value of DNR , suggesting that this agent is a competitive inhibitor of DNR transport.”

“The purpose of this work was 2-fold: (i) to investigate the mechanism by which genistein inhibits the DNR efflux in the GLC4/ADR cells; and (ii) to characterize the dependence of DNR transport on ATP concentration in intact GLC4/ADR cells.”

“ Genistein inhibited the enhanced DNR efflux in the GLC4/ADR cells.”

“Consistent with broad substrate specificity, the drug glutathione conjugate APA-SG, oxidized glutathione, the LTD4 antagonist MK571, arsenate, and genistein were competitive inhibitors of daunorubicin transport, with Ki values of 32 microM, 25 microM, 1.9 microM, 108 microM, and 23 microM, respectively.”