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Environ Toxicol Pharmacol. 2018 Oct;63:29-33. doi: 10.1016/j.etap.2018.08.007. Epub 2018 Aug 13.

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

Author information

1
Department of Nutrition, The Second School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China; Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
2
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
3
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
4
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address: cyzhong@njmu.edu.cn.

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.

KEYWORDS:

AP-1; Cell proliferation; MAPK; Phthalates; Prostate cancer

PMID:
30125794
DOI:
10.1016/j.etap.2018.08.007
[Indexed for MEDLINE]

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