engleski

Effects of the concomitant use of Δ9- tetrahydrocannabinol and the cytostatic irinotecan on cholinesterase activities in a mouse syngeneic model of colon cancer

Colorectal cancer patients treated with irinotecan (IRI) often manifest acute cholinergic syndrome, which is the reason behind the growing use of legally prescribed cannabis preparations as well as illicit ones that can contain very high Δ9- tetrahydrocannabinol (THC) levels. IRI-induced cholinergic syndrome originates from the inhibition of acetylcholinesterase (AChE), while butyrylcholinesterase (BChE) plays an important role in the hydrolytic metabolism of this prodrug. On the other hand, existing reports of THC effects on cholinesterases are inconclusive. In this study, we aimed to investigate how the concomitant use of a high THC dose with IRI affects cholinesterase activities in blood of mice with experimental colon cancer induced by injection of CT26 cell line. Male BALB/c mice were assigned randomly to five study groups: (i) negative control, (ii) cancer control, (iii) irinotecan (i.p. 60 mg/kg ; 1st and 5th day of the experiment), (iv) THC (p.o. 7 mg/kg ; repeatedly for 7 days), (v) IRI + THC. ChE activity in blood was assayed by the spectrophotometric Ellman method, using acetylthiocholine as a substrate and inhibitors to distinguish between AChE and BChE activities. The results showed a time-dependent increase in total ChE and BChE activities in all experimental groups, including cancer control. In contrast, AChE activities decreased, with some minor fluctuations in the THC and IRI+THC group. Although there was a lack of statistically significant differences, the time course of changes for AChE and BChE activities suggested that these esterases may not only be indicators of metabolic status but also functionally important in neoplastic cell transformation.

acetylcholinesterase ; blood ; butyrylcholinesterase ; cannabis ; tumorigenesis

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