Biological activity of oxygenated pinene derivatives on human colon normal and carcinoma cells

Abstract

AbstractThe antitumour activity of the oxygenated derivatives of pinene is still poorly understood. We hypothesized that the derivatives of pinene, (−)‐myrtenol, (−)‐myrtanol, and (−)‐myrtenal, would express different effects on human colon tumour cells and normal intestinal cells in vitro. For cytotoxic and nitric oxide (NOx) assays, human colon tumour (HT29) and human normal colon epithelial cells (CCD 841 CoTr) were incubated for 24 h with 0.1–5.0 mM of the terpenoids. The NOx level was determined in cells pre‐incubated or not with lipopolysaccharide (LPS). All three terpenoids decreased the activity of succinate dehydrogenase in tumour and normal cells, with a mixture (1 : 1 : 1) of the pinene derivatives having the strongest effect (with half‐maximal inhibitory concentrations, IC50, of 2.56 and 1.05 mM, respectively). The cytotoxic effect of the terpenes on tumour cells was observed at concentrations higher than 2 mM, with (–)‐myrtenal exerting the strongest activity (IC50 = 5.3 mM). Normal cells were more sensitive to the activity of the terpenes, especially when administered as a mixture (IC50 = 0.08 mM). The terpenoids synergistically stimulated tumour cells for NOx release and acted antagonistically in the case of normal cells. Tumour cells released the highest (1.111 μM) and normal cells released the lowest (0.146 μM) quantities of NOx after incubation with 1 mM terpenoid mixture. LPS‐induced tumour cells produced higher quantities of NOx than the unstimulated culture. An opposite effect was observed for normal intestinal cells. The investigated pinene derivatives inhibit the activity of human colon tumour cells in vitro by affecting mitochondrial enzyme activity, NOx release, and membrane stability. Differences in the bioactivity of the individual compounds can be determined on the basis of their structure and degree of oxidation.