6-OH-BDE-47 inhibited proliferation of skin fibroblasts from pygmy killer whale by inducing cell cycle arrest.

Tong Li, Yajing Sun, Ying Zeng, Edmond Sanganyado, Bo Liang, Wenhua Liu

The Science of the total environment 2022 Feb 10

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Hydroxylated polybrominated diphenyl ethers (OH-BDEs) are major transformation products of PBDEs that readily bioaccumulate in the marine food web. Although 6-OH-BDE-47 is frequently and abundantly detected in cetaceans, its potential toxic effects are largely unknown. We explored the toxicological pathways and mechanisms of OH-BDEs by exposing pygmy killer whale skin fibroblast cell lines (PKW-LWHT) to 6-OH-BDE-47 at concentrations ranging from 0.02, 0.2, 2 to 4 μM. The result showed that 6-OH-BDE-47 inhibited cell proliferation in a concentration- and time-dependent manner. The cell cycle data revealed that the cell cycle was arrest at the G0/G1 phase by 6-OH-BDE-47. Using qPCR and Western blot assay, we found that 6-OH-BDE-47 up-regulated the transcription and expression level of p21 and RB1 and down-regulated the expression level of Proliferating Cell Nuclear Antigen (PCNA), CDK2, CDK4, cyclin D1, cyclin E2, E2F1, and E2F3 and the cellular phosphorylated RB1. The results showed that 6-OH-BDE-47 was able to arrest the cell cycle of PKW-LWHT cells at G1 phase by changing the expression level of related regulatory genes in G1 stage, and finally inhibit cell proliferation. Copyright © 2021 Elsevier B.V. All rights reserved.

Citation

Tong Li, Yajing Sun, Ying Zeng, Edmond Sanganyado, Bo Liang, Wenhua Liu. 6-OH-BDE-47 inhibited proliferation of skin fibroblasts from pygmy killer whale by inducing cell cycle arrest. The Science of the total environment. 2022 Feb 10;807(Pt 1):150561