Dihydrorotenone (DHR) is a natural pesticide used for farming including organic produces. We recently found that Dihydrorotenone induces human plasma cell apoptosis by provoking endoplasmic reticulum stress. METHODS AND RESULTS: In the present study, we found that Dihydrorotenone arrested human plasma cancer cells at the G0/G1 phase of the cell cycle. Dihydrorotenone inhibited cyclin D2 transactivation, thus inhibiting its mRNA expression. In addition, Dihydrorotenone upregulated the cell cycle repressors p21 and p53. Dihydrorotenone also increased the phosphorylation level of p53, suggesting the upregulated transactivation function of p53, which was confirmed by the induction of p21, a substrate of activated p53. Moreover, Dihydrorotenone downregulated AKT and ERK phosphorylation, an incentive of cell cycle progression.
CONCLUSIONS:
Therefore, these results collectively demonstrated that Dihydrorotenone disrupts the cell cycle progress, which suggests that Dihydrorotenone is toxic to human plasma cells. Caution is thus suggested when handling with this agent. |