The dual effects of delta(9)-tetrahydrocannabinol on cholangiocarcinoma cells: anti-invasion activity at low concentration and apoptosis induction at high concentration.
Currently, only gemcitabine plus platinum demonstrates the considerable activity for cholangiocarcinoma. The anticancer effect of Delta (9)-tetrahydrocannabinol (THC), the principal active component of cannabinoids has been demonstrated in various kinds of cancers. We therefore evaluate the antitumor effects of THC on cholangiocarcinoma cells. Both cholangiocarcinoma cell lines and surgical specimens from cholangiocarcinoma patients expressed cannabinoid receptors. THC inhibited cell proliferation, migration and invasion, and induced cell apoptosis. THC also decreased actin polymerization and reduced tumor cell survival in anoikis assay. pMEK1/2 and pAkt demonstrated the lower extent than untreated cells. Consequently, THC is potentially used to retard cholangiocarcinoma cell growth and metastasis.
Leelawat
Surang
S
Faculty of Pharmacy, Rangsit University, Patumthani, Thailand. surangleelawat@gmail.com
Leelawat
Kawin
K
Narong
Siriluck
S
Matangkasombut
Oraphan
O
D023102:Anoikis / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000473:pathology; D003599:Cytoskeleton / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D013759:Dronabinol; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases