Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan
We are very interested in the hypothesis of Hoffman et al., that the intracellular redox potential E, given from the intracellular concentrations of [GSSG]/[GSH] (the oxidized and reduced forms of glutathione, respectively) may regulate the phosphorylation state of RB protein, and thereby governs the cell-cycle progression. Although the action mechanisms by which zerumbone (ZER) preferentially suppresses cancer cell proliferation has yet to be elucidated (1), it may be of help to take the hypothesis by Hoffman et al. indicating that there is a significant difference in the E value (10 mV) between proliferating fibroblasts and fibrosarcoma cells. A possible effect of ZER to reduce the intracellular [GSH], deduced by its chemical nature (i.e., Michael reaction acceptor), may make cancer, but not normal, cells reach their threshold E values where RB phosphorylation is attenuated to stop cell cycle. To test this hypothesis, it is necessary to perform some additional experiments. (i) Measurement of the intracellular [GSSG]/[GSH] of some normal and cancer cell lines which are treated, or not treated, with ZER. (ii) Exploration of the relationships among the E values, phosphorylation states of RB protein and cell growth rates. (iii) Confirmation of the production of an intracellular GSHZER adduct.
Notes
Email: ohigashi{at}kais.kyoto-u.ac.jp
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