We reported previously that panaxydol, a component of Panax ginseng roots, induced mitochondria-mediated apoptosis preferentially in transformed cells. This study demonstrates that EGFR activation and the resulting ER stress mediate panaxydolinduced apoptosis, and that panaxydol suppresses in vivo tumor growth in syngeneic and xenogeneic mouse tumor models. In addition, we elucidated that CaMKII and TGF-b-activated kinase (TAK1) Ginsenoside and C17 polyacetylenic compounds of Panax ginseng (P. ginseng C.A. Meyer, Korean ginseng) roots possess anticancer activities. [1][2][3][4] It has been shown that panaxydol (heptadeca-1-en-4,6-diyn-9,10-epoxy-3-ol), one of the C17 polyacetylenic compounds of P. ginseng, induces G1 cell cycle arrest or apoptosis in cancer cells depending on the concentration. 4,5 We also previously reported that the mechanisms of panaxydol-induced apoptosis involve a rapid increase in the cytoplasmic Ca 21 concentration ([Ca 21 ]c), activating NADPH oxidase via p38/JNK. NADPH oxidase activation induces oxidative stress and triggers mitochondria-dependent apoptosis. 5Transfer of excess Ca 21 from the endoplasmic reticulum (ER) to the mitochondria is an important mechanism in mitochondria-dependent apoptosis. It is postulated that ER Ca 21 is transferred via the mitochondria-associated ER