To investigate if the identified AMPK activator hernandezine can exhibit cytotoxic effects towards apoptosis-resistant cells, we adopted a panel of apoptosis-defective or apoptosis-resistant cells such as caspase 3/−7/−8 deficient MEFs, Bax-Bak double knockout (DKO) MEFs and DLD-1 Bax-Bak DKO human colon cancer cells as the cellular models. This evidence concerns the gene BAK1 and malignant colon neoplasm.