Abstract
Aim: We hypothesized that the anticancer activity of cannabinoids was linked to induction of phosphatases. Materials and Methods: The effects of cannabidiol (CBD) and the synthetic cannabinoid WIN-55,212 (WIN) on LNCaP (prostate) and SW480 (colon) cancer cell proliferation were determined by cell counting; apoptosis was determined by cleavage of poly(ADP)ribose polymerase (PARP) and caspase-3 (Western blots); and phosphatase mRNAs were determined by real-time PCR. The role of phosphatases and cannabinoid receptors in mediating CBD- and WIN-induced apoptosis was determined by inhibition and receptor knockdown. Results: CBD and WIN inhibited LNCaP and SW480 cell growth and induced mRNA expression of several phosphatases, and the phosphatase inhibitor sodium orthovanadate significantly inhibited cannabinoid-induced PARP cleavage in both cell lines, whereas only CBD-induced apoptosis was CB1 and CB2 receptor-dependent. Conclusion: Cannabinoid receptor agonists induce phosphatases and phosphatase-dependent apoptosis in cancer cell lines; however, the role of the CB receptor in mediating this response is ligand-dependent.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3799-3807 |
| Number of pages | 9 |
| Journal | Anticancer Research |
| Volume | 31 |
| Issue number | 11 |
| State | Published - Nov 2011 |
Keywords
- Apoptosis
- Cannabinoids
- Dual-specificity phosphatases
- Prostate cancer cell lines
- Protein tyrosine phosphatases
ASJC Scopus subject areas
- Oncology
- Cancer Research