Norcantharidin exhibits cytotoxicity in many
cancer cell lines, including
colorectal cancer (CRC) cells. Its cytotoxic potency on primary CRC cells and other normal constituent cells of the human body remains elusive. This study investigates whether
norcantharidin differentially exhibits cytotoxicity on primarily isolated CRC cells and dermal fibroblasts. The in vitro chemosensitivity of
norcantharidin was measured using a
MTT tetrazolium assay and compared with 73 primary
tumor cells from surgically excised
colorectal tumors, six human CRC cell lines and dermal fibroblasts. Observations of cytotoxicity to primary
tumor cells reveal significant differences among genders and histological types; however,
drug-induced chemosensitivity was not correlated with age or clinical stages of CRC patients.
Norcantharidin had a similar cytotoxic effect on primary
tumor cells and CRC cell lines in a dose-dependent manner. In contrast, normal fibroblasts were more resistant to
norcantharidin-induced cytotoxicity than CRC cells.
DAPI staining results demonstrated that
norcantharidin caused CRC cell apoptosis by nuclear fragmentation and
chromatin condensation. The release of
cytochrome c and the triggering of
caspase-3, -8 and -9 activation mediated apoptotic induction. Conversely, pretreatment with
caspases or
mitogen-activated protein kinase (MAPK) inhibitors significantly suppressed
norcantharidin-induced CRC cytotoxicity. These in vitro results suggest that
norcantharidin may be a safe and effective anti-
cancer drug for CRC.