4‐nitrophenol exposure in T24 human bladder cancer cells promotes proliferation, motilities, and epithelial‐to‐mesenchymal transition

Abstract

Although health hazards of 4‐nitrophenol (PNP) exposure have been reported, the adverse effects of PNP exposure on cancer biological features are still unknown. We investigated the effects of administration of PNP in T24 human bladder cancer cells. The results showed that PNP exposure promoted cellular proliferation, migration and invasion, inhibited adhesion and apoptosis in vitro. Using quantitative real‐time PCR, we found that (1) the mRNA expression levels of cell‐cycle regulators PCNA, cyclin D1 and COX‐2 were increased in PNP‐treated cells compared to controls, however, that of pro‐apoptotic gene Bax was decreased; (2) the expression level of EMT‐associated gene E‐cadherin was decreased in PNP‐treated cells, whereas those of N‐cadherin, vimentin, snail, and slug were increased; (3) the expression levels of cancer‐promoting genes HIF‐1, IL‐1β, VEGFα and K‐Ras were enhanced, but those of tumor suppressors p53, PTEN and BRCA were decreased. There was a positive association between PNP exposure times and the promotion effects. Finally, we found that the expression level of PPARγ (γ1 isoform) was increased in PNP‐treated T24 cells. GW9662, a specific PPARγ antagonist, attenuated PNP‐induced cell migration and invasion. These findings indicate that PNP exposure may promote bladder cancer growth and progression involving PPARγ signaling. PPARγ is a potential target for development of novel intervention study on environment pollution. Environ. Mol. Mutagen. 61:316–328, 2020. © 2019 Wiley Periodicals, Inc.

Overexpression of the PPAR‑γ protein in primary Ta/T1 non‑muscle‑invasive urothelial carcinoma

“…PPAR-γ ligands are expected to become promising therapeutic agents for chemoprevention and treatment. However, previous studies on PPAR-γ activation using several agonists have not provided consistent findings, such as the tumor suppressive or oncogenic role of PPAR-γ, in a heterogeneous nature in bladder cancer ( 9 , 10 ). Furthermore, limited information is currently available on the expression of PPAR-γ in carcinoma in situ (CIS), such as flat carcinoma.…”

PPAR-γ Modulators as Current and Potential Cancer Treatments

“…Metabolic-wise, researchers have found that the activation of PPAR-g could improve glucose and lipid metabolism, proving for the high demand of energy in the proliferation, migration and invasion of human prostate cancer cells and mice model (52). Interestingly, regarding factors involved in cell cycle, another study has found that the pro-apoptotic genes c-Myc and Bax are inhibited while cell-cycle regulators PCNA, cyclin D1 and COX-2 are promoted along with PPAR-g activation (40,55). In several studies, with the cell culture of human renal cell carcinoma, human prostate cancer xenografts in nude mice, as well as brain cancer in vivo, the increased expression of PPAR-g are all prognostically negative and pro-metastatic (56)(57)(58).…”

Exposure assessment of 170 pesticide ingredients and derivative metabolites in people from the Central Andes of Peru

“…Through chronic sublethal exposure, methomyl is also a strong genotoxic agent that induces DNA damage and cytotoxicity 38 . Likewise, PNP is an endocrine disruptor that has oncogenic potential 39 . PNP has been reported to exert hepatotoxic effects in rodents by increasing liver transcription levels of genes encoding the estrogen receptor-α, glutathione S-transferase, and www.nature.com/scientificreports/ aryl hydrocarbon receptor signaling pathway 40 .…”