Evidence has shown that
m-THPC and
verteporfin (VP) are promising sensitizers in
photodynamic therapy (
PDT). In addition, autophagy can act as a
tumor suppressor or a
tumor promoter depending on the
photosensitizer (PS) and the
cancer cell type. However, the role of autophagy in
m-THPC- and VP-mediated
PDT in in vitro and in vivo models of human
colorectal cancer (CRC) has not been reported. In this study,
m-THPC-
PDT or VP-
PDT exhibited significant
phototoxicity, inhibited proliferation, and induced the generation of large amounts of
reactive oxygen species (ROS) in CRC cells. From immunoblotting, fluorescence image analysis, and transmission electron microscopy, we found extensive autophagic activation induced by ROS in cells. In addition,
m-THPC-
PDT or VP-
PDT treatment significantly induced apoptosis in CRC cells. Interestingly, the inhibition of
m-THPC-
PDT-induced autophagy by knockdown of ATG5 or ATG7 substantially inhibited the apoptosis of CRC cells. Moreover,
m-THPC-
PDT treatment inhibited
tumorigenesis of subcutaneous HCT116 xenografts. Meanwhile,
antioxidant treatment markedly inhibited autophagy and apoptosis induced by
PDT in CRC cells by inactivating JNK signaling. In conclusion, inhibition of autophagy can remarkably alleviate
PDT-mediated anticancer efficiency in CRC cells via inactivation of the ROS/JNK signaling pathway. Our study provides evidence for the therapeutic application of
m-THPC and VP in CRC.