Phthalates promote prostate cancer cell proliferation through activation of ERK5 and p38.

Abstract

Prostate cancer is one of the most commonly diagnosed cancers in man. Studies have shown that phthalates may act as promoters in various types of cancer; however, the role of phthalates in prostate cancer has been rarely reported. The MAPK/AP-1 pathway is a vital regulator of cell proliferation in cancer. In this report we found that three typical phthalates, diethylhexyl phthalate (DEHP), Butyl benzyl phthalate (BBP) and Dibutyl phthalate (DBP), up-regulated cyclinD1 and PCNA, down-regulated P21, inducing proliferation of prostate cancer cells. Furthermore, we found that phthalates increased the expression of p-ERK5 and p-p38, along with upregulation of AP-1 (p-c-fos and p-c-jun). In studies with ERK5 and a p38 inhibitor, our data showed that downregulation of p-ERK5 or p38 inhibited phthalate-triggered cell proliferation. Taken together, findings from this study suggest that phthalates activate MAPK/AP-1 pathway and may potentially promote cell proliferation in prostate cancer, thus providing new insight into the effects and the underlying mechanism of phthalates on prostate cancer.

• Authors: Mingming Zhu, Cong Huang, Xiao Ma, Rui Wu, Weiwei Zhu, Xiaoting Li, Zhaofeng Liang, Feifei Deng, Jieshu Wu, Shanshan Geng, Chunfeng Xie, Caiyun Zhong
• Journal: Environmental toxicology and pharmacology (Environ Toxicol Pharmacol) Vol. 63 Pg. 29-33 (Oct 2018) ISSN: 1872-7077 [Electronic] Netherlands
• PMID: 30125794 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• CCND1 protein, human
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• PCNA protein, human
• Phthalic Acids
• Proliferating Cell Nuclear Antigen
• Cyclin D1
• Dibutyl Phthalate
• Diethylhexyl Phthalate
• Mitogen-Activated Protein Kinase 7
• p38 Mitogen-Activated Protein Kinases
• butylbenzyl phthalate

Topics

• Cell Line, Tumor
• Cell Proliferation
• Cyclin D1 (genetics)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics)
• Dibutyl Phthalate (toxicity)
• Diethylhexyl Phthalate (toxicity)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• MAP Kinase Signaling System (drug effects)
• Male
• Mitogen-Activated Protein Kinase 7 (metabolism)
• Phosphorylation (drug effects)
• Phthalic Acids (toxicity)
• Proliferating Cell Nuclear Antigen (genetics)
• Prostatic Neoplasms (chemically induced, metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)