Apoptosis-inducing action of two products from oxidation of sesamol, an antioxidative constituent of sesame oil: a possible cytotoxicity of oxidized antioxidant.
Many effects of sesamol, an antioxidative constituent of sesame oil, have been reported for human health benefits due to its antioxidative action. However, we recently isolated two cytotoxic products, trimer and tetramer of sesamol, from oxidation of sesamol by an assay-guided purification. In this study, we have revealed some cytotoxic characteristics of these products in rat thymocytes and human leukemia K562 cells. Incubation of cells with trimer or tetramer at 10-30 microM for 24h significantly increased cell lethality and population of rat thymocytes containing hypodiploid DNA, suggesting cell death with DNA fragmentation, while it was not the case for 30 microM sesamol. The cytotoxic action of tetramer was more potent than that of trimer in rat thymocytes when their concentrations were 10-30 microM. The incubation of cells with 10 microM tetramer for 24h increased the population of cells with exposed phosphatidylserine, the activity of caspases, and the nick of DNA. These results indicate tetramer-induced apoptosis. In K562 cells, the incubation with tetramer at 10 microM for 72 h significantly inhibited the growth without affecting the lethality. However, tetramer at 30 microM significantly increased cell lethality. It is likely that tetramer exerts more cytotoxic action on normal non-proliferative cells (rat thymocytes) rather than proliferative cancer cells (human leukemia K562 cells). It may be necessary to consider the condition for preservation of sesamol and the safety of products from in vivo oxidation of sesamol for human health.
Laboratories of Bioorganic Chemistry and Cellular Signaling, Faculty of Integrated Arts and Sciences, The University of Tokushima, Tokushima, Japan.
Aya
A
Fujimoto
Yoshimi
Y
Shingai
Toshihisa B
TB
Oyama
Takuya
T
Kawanai
Erika
E
Hashimoto
Kazuki
K
Koizumi
Kaori
K
Kimura
Toshiya
T
Masuda
Yasuo
Y
Oyama
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D052117:Benzodioxoles / Q000737:chemistry / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D005591:Chemical Fractionation; D006801:Humans; D020014:K562 Cells; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012715:Sesame Oil / Q000737:chemistry*; D013950:Thymus Gland / Q000166:cytology
D000975:Antioxidants; D052117:Benzodioxoles; D010636:Phenols; D012715:Sesame Oil; C025583:sesamol