The Dual Effects of Δ⁹-Tetrahydrocannabinol on Cholangiocarcinoma Cells: Anti-Invasion Activity at Low Concentration and Apoptosis Induction at High Concentration

Abstract

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.

Δ9Tetrahydrocannabinol attenuates Staphylococcal enterotoxin B‐induced inflammatory lung injury and prevents mortality in mice by modulation of miR‐17‐92 cluster and induction of T‐regulatory cells

“…Our results demonstrate the derepression of Pten suggesting that THC, via the down‐regulation of the cluster might be an inhibitor of the PI3K/Akt pathway. Interestingly, earlier studies in cancer models have demonstrated that THC disrupts the PI3K/Akt signalling pathway (Greenhough et al ., ; Leelawat et al ., ). However, in light of our current observation that it modulates key miRNA, its anti‐inflammatory properties via its role as a PI3K/Akt inhibitor are made more evident.…”

Compromised External Validity: Federally ProducedCannabisDoes Not Reflect Legal Markets

“…Particularly as cannabinoids can have dramatic opposing effects and complex interactions with each other 11,12,[14][15][16][17][18][19][20][21] , investigations that only use one source of material may hinder our understanding of pharmacological and therapeutic effects of Cannabis. Given that the effects of Cannabis may vary depending upon the dose 39,40 , where both the chemotype and the dose are important in the medical effects 41,42 , and the potential harmful effects 12 , it is crucial for scientific and medical investigations to access the varieties used by patients and recreational users.…”

Cannabinoids as anticancer drugs: current status of preclinical research

“…In another investigation, siRNA, inhibitor and add-back experiments showed that the cannabinoid receptor- and TRPV1-dependent downregulation of plasminogen activator inhibitor (PAI)-1 in CBD-exposed lung cancer cells [ 103 ] is part of the anti-invasive effect of this cannabinoid, in addition to the upregulation of TIMP-1 mentioned above. Still other work revealed that the anti-invasive effect of THC on cholangiocarcinoma cells is associated with reduced activation of Akt and p42/44 MAPK [ 104 ]. Furthermore, a very recent work found that treatment with CBD in combination with THC or CBD alone inhibited bladder urothelial carcinoma cell migration independently of cannabinoid receptors [ 105 ].…”