Comparative cytotoxicity and ROS generation by curcumin and tetrahydrocurcumin following visible-light irradiation or treatment with horseradish peroxidase.
In order to clarify the cytotoxic mechanism of curcumin, a well-known chemopreventive agent, the cytotoxicity (by MTT method), intracellular glutathione (using GSH detection kit) and intracellular reactive oxygen species (ROS) levels (with a flow cytometer), were measured in curcumin- and tetrahydrocurcumin (TH-curcumin)-treated cancer (HSG) and normal (HGF) cells under two different oxidation conditions: irradiation with visible light (VL) and enzymatic oxidation with horseradish peroxidase (HRP)/H2O2. The cytotoxicity of curcumin was highly enhanced by VL-irradiation, whereas that of TH-curcumin was enhanced by HRP/H2O2 treatment. The cytotoxicity of curcumin against HGF cells was greater than that against HSG cells. Curcumin significantly reduced the intracellular GSH level significantly under VL-irradiation, and increased it under HRP/H2O2, whereas TH-curcumin had no effect with either oxidation treatment. HRP/H2O2 treatment of TH-curcumin enhanced generation of ROS; in contrast, VL-irradiation of curcumin was considered to produce ROS preferably. In conclusion, curcumin was highly photo-toxic, caused a decrease in GSH and mediated ROS generation. In contrast, the cytotoxicity of TH-curcumin was enhanced by enzymatic oxidation. A low-level pro-oxidant intracellular milieu induced by TH-curcumin could be effectively useful for cancer prevention.
Atsumi
Toshiko
T
Division of Physiology, Department of Human Development and Fostering, Meikai University School of Dentistry, 1-1, Keyakidai, Sakado-shi, Saitama 350-0283, Japan. tosi@dent.meikai.ac.jp
Tonosaki
Keiichi
K
Fujisawa
Seiichiro
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002648:Child; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005881:Gingiva / Q000166:cytology; D005978:Glutathione / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008027:Light; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; C096277:tetrahydrocurcumin; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D005978:Glutathione; D003474:Curcumin