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). The gene discussed is RPS6KA1; the disease is melanoma.