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Natural Pesticide Dihydrorotenone Arrests Human Plasma Cancer Cells at the G0/G1 Phase of the Cell Cycle
Author(s) -
Xu Xin,
Zhang Jieyu,
Han Kunkun,
Zhang Zubin,
Chen Guodong,
Zhang Jinping,
Mao Xinliang,
Cao Biyin
Publication year - 2014
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21558
Subject(s) - cell cycle , transactivation , microbiology and biotechnology , cyclin a , cell cycle checkpoint , downregulation and upregulation , mapk/erk pathway , chemistry , cell growth , kinase , protein kinase b , cyclin , phosphorylation , apoptosis , biology , biochemistry , transcription factor , gene
Dihydrorotenone (DHR) is a natural pesticide used for farming including organic produces. We recently found that DHR induces human plasma cell apoptosis by provoking endoplasmic reticulum stress. In the present study, we found that DHR arrested human plasma cancer cells at the G0/G1 phase of the cell cycle. Mechanistical studies demonstrated that cell cycle arrest was associated with downregulated cell cycle promotors including cyclin D2, cyclin D3, cyclin‐dependent kinases (CDK4, CKD6), and phosphorylated‐Rb. DHR inhibited cyclin D2 transactivation, thus inhibiting its mRNA expression. In addition, DHR upregulated the cell cycle repressors p21 and p53. DHR 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, DHR downregulated AKT and ERK phosphorylation, an incentive of cell cycle progression. Therefore, these results collectively demonstrated that DHR disrupts the cell cycle progress, which suggests that DHR is toxic to human plasma cells. Caution is thus suggested when handling with this agent.