The following molecules are known to naturally inhibit VEGF signaling, thereby impeding CSCs metastasis: 1) Vitamin C inhibits VEGF signaling through degrading HIF-1α (Zhao et al., 2020); and 2) Melatonin (MLT), a natural pineal gland hormone, regulates neoangiogenesis and inhibits lung and breast cancer cells through the downregulation of HIF-1α/ROS/VEGF (Cheng et al., 2019). The gene discussed is VEGFA; the disease is breast carcinoma.