Department of Nutrition and Dietetics, Faculty of Health Sciences, Bezmialem Vakif University, Silahtarağa Caddesi No: 189, Eyüp, 34065, Istanbul, Turkey.
Department of Medical Biochemistry, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
Mol Cell Biochem. 2018 Nov;448(1-2):237-249. doi: 10.1007/s11010-018-3329-5. Epub 2018 Feb 13.
Carvacrol is a natural phenolic compound found in essential oils of Lamiaceae species. In the present study, an attempt has been made to elucidate the mechanism behind the anti-cancer potential of carvacrol on human gastric adenocarcinomas (AGS) by comparing its effects on cancer cells AGS to those on normal human fibroblast (WS-1) cells, in vitro. Cytotoxicity, reactive oxygen species (ROS) generation, glutathione (GSH) levels, genotoxicity, and apoptotic effects of carvacrol (0-600 µM) were studied in both cell lines. Additionally, the effect of high dose carvacrol (100 mg/kg BW) on the oxidative status was investigated in vivo. For this purpose, carvacrol was administered orally to male Wistar rats over a period of 60 days. Rats were weighed regularly. At the end of the experiment, rats were euthanized. Blood and stomach tissues were collected for biochemical and pathological examinations. The in vitro results showed significant differences in cell viability of AGS compared to WS-1 cells exposed to carvacrol. Also the extent of ROS generation, GSH reduction and DNA damage differed significantly between the cell lines studied (P ≤ 0.001). The differences observed were statistically significant at all concentrations applied (P ≤ 0.001). The results found in AGS cells were mirrored in the pathohistological findings obtained from animals of the in vivo experimental group. Changes in body weight, and oxidative stress index for plasma and stomach tissues of animals in this group were found to differ statistically significant from those found in the control group of Wistar rats (P ≤ 0.001). The data obtained from our present study uncovered that carvacrol has the potential to cause toxic effects in both, AGS and WS-1 cells but more effectively in cancer cells than in normal cells. The carvacrol-mediated responses observed in the in vitro and in vivo experiments presented suggest a double-edged pro-oxidative effect. Via this mechanism carvacrol induced cytotoxicity, apoptosis, and DNA damage in a dose-dependent manner in both cancer and normal cells and these activities were higher in cancer cells than those of normal cells.
香芹酚是唇形科植物精油中的一种天然酚类化合物。在本研究中，通过比较香芹酚对人胃腺癌（AGS）细胞和正常人类成纤维细胞（WS-1）的作用，试图阐明其抗癌潜力的机制。在这两种细胞系中，研究了香芹酚（0-600 μM）的细胞毒性、活性氧（ROS）生成、谷胱甘肽（GSH）水平、遗传毒性和凋亡作用。此外，还在体内研究了高剂量香芹酚（100mg/kgBW）对氧化状态的影响。为此，将香芹酚口服给予雄性 Wistar 大鼠，持续 60 天。定期称量大鼠体重。实验结束时，处死大鼠。采集血液和胃组织进行生化和病理检查。体外结果表明，与 WS-1 细胞相比，AGS 细胞对香芹酚的细胞活力有显著差异。ROS 生成、GSH 减少和 DNA 损伤的程度在研究的细胞系之间也有显著差异（P≤0.001）。在所有应用浓度下，观察到的差异均具有统计学意义（P≤0.001）。体内实验组动物的组织病理学结果反映了 AGS 细胞中观察到的结果。与 Wistar 大鼠对照组相比，该组动物的体重变化以及血浆和胃组织的氧化应激指数存在统计学显著差异（P≤0.001）。本研究获得的数据表明，香芹酚有可能在 AGS 和 WS-1 细胞中引起毒性作用，但在癌细胞中的作用比在正常细胞中更为有效。在体外和体内实验中观察到的香芹酚介导的反应表明其具有双重促氧化作用。通过这种机制，香芹酚以剂量依赖的方式在癌细胞和正常细胞中诱导细胞毒性、凋亡和 DNA 损伤，其活性在癌细胞中高于正常细胞。
