TY - JOUR
T1 - 6-OH-BDE-47 inhibited proliferation of skin fibroblasts from pygmy killer whale by inducing cell cycle arrest
AU - Li, Tong
AU - Sun, Yajing
AU - Zeng, Ying
AU - Sanganyado, Edmond
AU - Liang, Bo
AU - Liu, Wenhua
N1 - Funding Information:
The authors gratefully acknowledge the financial support by the National Science Foundation for Young Scientists of China (Grant No. 42006105) and Ministry of Agriculture (Chinese White Dolphin Conservation Action), CNOOC Foundation, and Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (grant number GML2019ZD0606).
PY - 2022/2/10
Y1 - 2022/2/10
N2 - 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.
AB - 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.
KW - Cell cycle arrest
KW - Cell proliferation
KW - Dolphin
KW - Hydroxylated polybrominated diphenyl ethers (OH-BDEs)
KW - Skin fibroblast cell line
UR - http://www.scopus.com/inward/record.url?scp=85116259082&partnerID=8YFLogxK
U2 - 10.1016/j.scitotenv.2021.150561
DO - 10.1016/j.scitotenv.2021.150561
M3 - Article
C2 - 34624692
AN - SCOPUS:85116259082
SN - 0048-9697
VL - 807
JO - Science of the Total Environment
JF - Science of the Total Environment
M1 - 150561
ER -