The 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.

中文翻译：

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氧化pin烯衍生物对人结肠正常细胞和癌细胞的生物活性

pin的氧化衍生物的抗肿瘤活性仍然知之甚少。我们假设pin烯，（-）-myrtenol，（-）-myrtanol和（-）-myrtenal的衍生物在体外对人结肠肿瘤细胞和正常肠道细胞表达不同的作用。对于细胞毒性和一氧化氮（NOx）分析，将人结肠肿瘤（HT29）和人正常结肠上皮细胞（CCD 841 CoTr）与0.1–5.0 mM的萜类化合物一起孵育24小时。在未与脂多糖（LPS）一起预孵育的细胞中确定NOx的水平。所有三种萜类化合物均会降低肿瘤和正常细胞中的琥珀酸脱氢酶活性，其中（烯衍生物的混合物（1：1：1）具有最强的作用（抑制浓度为半数最大，IC _50）分别为2.56和1.05 mM）。在高于2 mM的浓度下观察到萜烯对肿瘤细胞的细胞毒性作用，其中（-）-肾上腺素发挥最强的活性（IC ₅₀  = 5.3 mM）。正常细胞对萜烯的活性更敏感，尤其是当以混合物的形式给药时（IC ₅₀ = 0.08 mM）。萜类化合物协同刺激肿瘤细胞释放NOx，在正常细胞的情况下具有拮抗作用。与1 mM萜类混合物温育后，肿瘤细胞释放的NOx最高（1.111μM），而正常细胞释放的NOx最低（0.146μM）。LPS诱导的肿瘤细胞比未刺激的培养物产生更多的NOx。对于正常肠细胞观察到相反的作用。所研究的pin烯衍生物通过影响线粒体酶活性，NOx释放和膜稳定性来抑制体外人结肠肿瘤细胞的活性。可以根据其化合物的结构和氧化程度确定其各自生物活性的差异。