Chlorpyrifos inhibits cell proliferation through ERK1/2 phosphorylation in breast cancer cell lines

Ventura, Clara; Venturino, Andrés; Miret, Noelia; Randi, Andrea; Rivera, Elena; Núñez, Myriam; Cocca, Claudia

doi:10.1016/j.chemosphere.2014.07.088

Cited by 59 publications

(25 citation statements)

References 30 publications

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“…However, another organophosphate, chlorpyrifos, which was associated with increased breast cancer risk in this study, has been observed to act as a potential endocrine disruptor in vivo ( Ventura et al 2016 ) and in vitro ( Andersen et al 2002 ), altering levels of circulating and bioavailable sex hormones ( Hodgson and Rose 2006 ). Chlorpyrifos also induces cell proliferation ( Ventura et al 2016 ), oxidative stress ( Ventura et al 2015 ), and genotoxicity ( Rahman et al 2002 ). However, a rodent bioassay of chlorpyrifos found no evidence of carcinogenicity ( Yano et al 2000 ).…”

Section: Discussionmentioning

confidence: 65%

Insecticide Use and Breast Cancer Risk among Farmers’ Wives in the Agricultural Health Study

Engel

Werder

Satagopan

et al. 2017

Environ Health Perspect

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Background:Some epidemiologic and laboratory studies suggest that insecticides are related to increased breast cancer risk, but the evidence is inconsistent. Women engaged in agricultural work or who reside in agricultural areas may experience appreciable exposures to a wide range of insecticides.Objective:We examined associations between insecticide use and breast cancer incidence among wives of pesticide applicators (farmers) in the prospective Agricultural Health Study.Methods:Farmers and their wives provided information on insecticide use, demographics, and reproductive history at enrollment in 1993–1997 and in 5-y follow-up interviews. Cancer incidence was determined via cancer registries. Among 30,594 wives with no history of breast cancer before enrollment, we examined breast cancer risk in relation to the women’s and their husbands’ insecticide use using Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).Results:During an average 14.7-y follow-up, 39% of the women reported ever using insecticides, and 1,081 were diagnosed with breast cancer. Although ever use of insecticides overall was not associated with breast cancer risk, risk was elevated among women who had ever used the organophosphates chlorpyrifos [HR=1.4 (95% CI: 1.0, 2.0)] or terbufos [HR=1.5 (95% CI: 1.0, 2.1)], with nonsignificantly increased risks for coumaphos [HR=1.5 (95% CI: 0.9, 2.5)] and heptachlor [HR=1.5 (95% CI: 0.7, 2.9)]. Risk in relation to the wives’ use was associated primarily with premenopausal breast cancer. We found little evidence of differential risk by tumor estrogen receptor status. Among women who did not apply pesticides, the husband’s use of fonofos was associated with elevated risk, although no exposure–response trend was observed.Conclusion:Use of several organophosphate insecticides was associated with elevated breast cancer risk. However, associations for the women’s and husbands’ use of these insecticides showed limited concordance. Ongoing cohort follow-up may help clarify the relationship, if any, between individual insecticide exposures and breast cancer risk. https://doi.org/10.1289/EHP1295

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Section: Discussionmentioning

confidence: 65%

Insecticide Use and Breast Cancer Risk among Farmers’ Wives in the Agricultural Health Study

Engel

Werder

Satagopan

et al. 2017

Environ Health Perspect

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“…Conventional MAPKs include p38 MAPK, extracellular signalregulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinases/stress activated protein kinases (JNK/SAPK) and ERK5 [Arthur and Ley, 2013]. Activation of p38 MAPK [Galliher and Schiemann, 2007;Jiang et al, 2016] and ERK1/2 [Ventura et al, 2015;Liu et al, 2016] pathways are important for breast cancer cell proliferation. Sathya et al [2015] found that estrogen suppressed breast cancer proliferation through inhibiting p38 MAPK signaling pathway.…”

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confidence: 99%

GLUL Promotes Cell Proliferation in Breast Cancer

et al. 2017

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Glutamate-ammonia ligase (GLUL) belongs to the glutamine synthetase family. It catalyzes the synthesis of glutamine from glutamate and ammonia in an ATP-dependent reaction. Here, we found higher expression of GLUL in the breast cancer patients was associated with larger tumor size and higher level of HER2 expression. In addition, GLUL was heterogeneously expressed in various breast cancer cells. The mRNA and protein expression levels of GLUL in SK-BR-3 cells were obviously higher than that in the other types of breast cancer cells. Results showed GLUL knockdown in SK-BR-3 cells could significantly decrease the proliferation ability. Furthermore, GLUL knockdown markedly inhibited the p38 MAPK and ERK1/ERK2 signaling pathways in SK-BR-3 cells. Thus, GLUL may represent a novel target for selectively inhibiting p38 MAPK and ERK1/ERK2 signaling pathways and the proliferation potential of breast cancer cells. J. Cell. Biochem. 118: 2018-2025, 2017. © 2016 Wiley Periodicals, Inc.

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“…However, two other studies did not find any chlorpyrifos-induced endocrine disrupting potential [ 47 , 48 ]. Chlorpyrifos was also found to alter changes in gene expression [ 46 ], induce cell cycle arrest in the S and G2/M-phase vent [ 49 ], decrease cell proliferation [ 50 ], and increase oxidative stress [ 51 ]. A detailed summary of the main findings and their proposed cellular mechanisms are shown in Table 3 .…”

Section: Resultsmentioning

confidence: 99%

Organophosphate Pesticide Exposure and Breast Cancer Risk: A Rapid Review of Human, Animal, and Cell-Based Studies

Yang

Lee

Park

2020

IJERPH

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Background: Organophosphate pesticides (OPs) are one of the most commonly used classes of insecticides in the U.S., and metabolites of OPs have been detected in the urine of >75% of the U.S. population. While studies have shown that OP exposure is associated with risk of neurological diseases and some cancers, the relationship between OP exposure and breast cancer risk is not well understood. Methods: The aim of this rapid review was to systematically evaluate published literature on the relationship between OP exposure and breast cancer risk, including both epidemiologic and laboratory studies. Twenty-seven full-text articles were reviewed by searching on Pubmed, EMBASE, and Cochrane databases. Results: Some human studies showed that malathion, terbufos, and chlorpyrifos were positively associated with human breast cancer risk, and some laboratory studies demonstrated that malathion and chlorpyrifos have estrogenic potential and other cancer-promoting properties. However, the human studies were limited in number, mostly included agricultural settings in several geographical areas in the U.S., and did not address cumulative exposure. Conclusions: Given the mixed results found in both human and laboratory studies, more research is needed to further examine the relationship between OP exposure and breast cancer risk, especially in humans in non-agricultural settings.

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Chlorpyrifos inhibits cell proliferation through ERK1/2 phosphorylation in breast cancer cell lines

Cited by 59 publications

References 30 publications

Insecticide Use and Breast Cancer Risk among Farmers’ Wives in the Agricultural Health Study

Insecticide Use and Breast Cancer Risk among Farmers’ Wives in the Agricultural Health Study

GLUL Promotes Cell Proliferation in Breast Cancer

Organophosphate Pesticide Exposure and Breast Cancer Risk: A Rapid Review of Human, Animal, and Cell-Based Studies

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