ERN1 and melanoma: In A375 and 451Lu human melanoma cells, fisetin induced endoplasmic reticulum (ER) stress, up‐regulated the ER stress markers (ATF4, XBP1s, IRE1α, and GRP78), and activated the extrinsic and intrinsic apoptotic pathways. Fisetin exhibited the autophagic response concomitant with induction of apoptosis, suppressed the progression, and increased cleaved caspase‐3.