HES1 and neoplasm: Ribosome-inactivating proteins (cucurmosins) and cucurbitacins from pumpkins induce cell-cycle arrest (G0/G1 or G2/M) and caspase-dependent apoptosis in various tumor cells (e.g. HER2+ breast, NSCLC, colorectal), while inhibiting oncogenic pathways (Notch–Hes1, PI3K/Akt/mTOR, STAT3) and activating AMPK (151, 152).