Colorectal carcinoma (CRC) is the third most common malignant
tumor pathology worldwide. Despite progress in
surgical procedures and
therapy options, CRC is still a considerable cause of
cancer-related mortality. In this study, we tested the antitumor effects of
shikonin in CRC and tried to identify its potential mechanism. The potential target, molecular mechanism as well as in vitro and in vivo antitumor effects of
shikonin in CRC cells were determined by an integrative protocol including quantitative proteomics, RT-PCR, western blotting, RNA interference and overexpression, apoptosis and autophagy assays, etc.
Galectin-1 was a potential target of
shikonin from the iTRAQ-based proteomic analysis in
shikonin-treated SW620 cell. The overexpression and RNA silencing of
galectin-1 in two CRC cells suggested that the
shikonin sensitivity was correlation to
galectin-1 levels. The ROS accumulation induced by
shikonin was important to the formation of
galectin-1 dimers. Dimer
galectin-1 was found to be associated with the activation of JNK and downstream apoptosis or autophagy. Moreover, through functional in vitro studies, we showed that differences in
galectin-1 level affected
tumor cell proliferation, migration, and invasion. In summary,
shikonin induced CRC cells apoptosis and autophagy by targeting
galectin-1 and JNK signaling pathway both in vitro and in vivo, which suggested a potential novel
therapy target for CRC.