This study was focused on the possible role and application of non-psychoactive Cannabis sativa L. extracts as antiproliferative agents, in particular in combination with conventional chemotherapy. The compounds present in different extracts from non-psychoactive C. sativa varieties were characterized by means of ultra high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) and their antiproliferative activity was assessed on different human cancer cell lines. The antiproliferative activity of the extracts was assessed on different human cancer cells of endodermal (HT29), mesodermal (K562, U937, Jurkat) and ectodermal (U87MG) origin. The results indicated that the K562 chronic myelogenous leukemia cell line was the one that responded better to the treatment and the CBD-type extract was the one that provided the lowest IC50 value (10 µg/mL). These cytotoxic effects were not observed in human non-cancer cells. The cytofluorimetric analysis revealed that the antiproliferative effect was mainly due to the induction of apoptosis, as shown by an increase of cell population annexin V positive, although at present apo-necrosis or autophagic activity can not be excluded. The analysis of the mechanical properties of the membrane bilayer, using liposomes, showed that both the CBD-type extract and the pure compound are able to increase the membrane flutuation without altering the phase transition of phospholipids, indicating that they interact with cell membrane, but they did not modulate the lipid raft composition. Finally, dose-response curves were built for the associations of the CBD-type extract at 5 µg/mL and CBD at 5 µM with anticancer drugs currently used in therapy, including vincristine, imatinib and doxorubicin at 48 h of treatment. The dose-response curves did not show a significant decrease of the IC50 value for imatinib and doxorubicin both in association with the extract and with pure CBD. Differently, vincristine associated with the CBD-type extract showed a 10 times higher efficacy then the vincristine alone. Since the pharmacological activity of vincristine is related to its micrutubule-destabilizing properties, the CBD-rich extract and pure CBD might act on the same target/s, thus enhancing the antiproliferative activity of this anticancer drug.

Chemical characterization of non-psychoactive Cannabis sativa L. extracts and evaluation of their antiproliferative activity

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.