The insights gained from this study include (i) fisetin mediated inhibition of YB-1 extends to other cancer cell types including melanoma and ovarian cancer cells (ii) fisetin binds to RSK2 avidly and this complex augments the binding of fisetin to YB-1 (iii) fisetin suppresses MDR1 downstream of YB-1 but inhibition does not translate into decreased substrate efflux (iv) fisetin mediated RSK suppression is independent of its effect on ERK signaling (Fig. 7). This evidence concerns the gene RPS6KA3 and melanoma.