Hydroquinone (HQ), one of the most significant metabolic activation products of
benzene in an organism, can cause hematological toxicity, such as
acute myeloid leukemia. It is a clear
carcinogen that can cause changes in the disorder of cell cycle and cell growth. However, its molecular mechanisms remain unclear. E4
transcription factor 1 (E4F1), an important
transcription factor, participating in the regulation of cell cycle may be related to the occurrence of
tumor. Here, we examined the HQ-induced malignant transformed TK6 cells (TK6-HT) to illustrate the role of E4F1 in
carcinogenesis. The present study showed that both the expressions of E4F1
messenger RNA and
protein increased obviously in TK6-HT, preliminarily indicating that E4F1 is associated with HQ-induced
carcinogenesis. To further explore the role of E4F1, we established E4F1 silencing TK6-HT (pLVX-shE4F1) and its control cells (pLVX-shNC) using lentiviral
short hairpin RNA (
shRNA) interference expression plasmid vector pLVX-
shRNA. Flow cytometry and cell counting kit-8 assay were used to determine the effects of E4F1 silencing on cell cycle and cell growth, respectively. E4F1 silencing inhibited cell growth in TK6-HT. The results from flow cytometry indicated that the inhibitory effect on cell growth may be the results of the E4F1 silencing-induced accumulation in G2/M compared with TK6-HT-shNC. Meanwhile, levels of DNA damage (γ-H2AX),
proteins of Rb and phosphorylated Rb, and
reactive oxygen species were increased in TK6-HT-shRNA2 cells, which is the critical reason of cell-cycle arrest. In conclusion, E4F1 silencing inhibits the cell growth through cell-cycle arrest in malignant transformed cells induced by HQ.