V‐ATPase inhibition has been shown to result in increased reactive oxygen species (ROS) in cancer cells75, 76, 77 and HIF1α upregulation.74 Furthermore, V‐ATPase inhibition induces caspase‐dependent apoptosis in invasive tumor cells via the mitochondrial pathways.74, 78 Archazolid was also shown to induce cell cycle arrest in MDA‐MB‐231 cells and double‐strand breaks in all cell lines investigated.79 This evidence indicates that V‐ATPase inhibition can induce a cellular stress response, autophagy, and eventually apoptosis in tumor cells. This evidence concerns the gene HIF1A and neoplasm.