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Aromatic monoterpene, thymol, shows several beneficial activities, such as an antioxidative effect. However, the mechanism of its toxicity remains to be fully defined. In preliminary studies, thymol was characterized as a melanin formation inhibitor in an enzymatic system; however, thymol showed moderate cytotoxicity but not an antimelanogenic effect on B16-F10 melanoma cells. Thymol exhibited cytotoxicity, with an IC(50) value of 400 μM (60.09 μg/mL). This moderate toxic effect was suppressed with the addition of vitamin C and vitamin D, and 20 and 40% of cell viability was increased, respectively. Subsequently, the treatment of L-cysteine on thymol-treated melanoma cells reversed the toxic effect of thymol. Moreover, a significant oxidative stress condition was observed when B16 melanoma cells were cultured with thymol. In conclusion, the antioxidant actions of thymol generate a stable phenoxy radical intermediate, which generates reactive oxygen species and quinone oxide derivatives. Thus, it is proposed that the primary mechanism of thymol toxicity at high doses is due to the formation of antioxidant-related radicals.


Hiroki Satooka, Isao Kubo. Effects of thymol on B16-F10 melanoma cells. Journal of agricultural and food chemistry. 2012 Mar 14;60(10):2746-52

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PMID: 22352891

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