This activation leads to PRODH/POX‐dependent ROS generation, initiating melanoma cell apoptosis.[135] Moreover, metformin inhibits the phosphorylation of Smad3 and disrupts its interaction with lysine acetyltransferase 5 (KAT5), thereby attenuating KAT5‐mediated K333 acetylation of Smad3. Here, SMAD3 is linked to melanoma.