Involvement of mitochondrial pathway in benzo[a]pyrene-induced neuron apoptosis

Js, Nie; Zhang, H; Zhao, Jinjin; Hj, Liu; Niu, Qiao

doi:10.1177/0960327113493301

Cited by 24 publications

(18 citation statements)

References 43 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The observed decrease in cellular proliferation in the presence of drugs is expected as one of the modes of action of the drugs is inhibition of cellular growth and the killing of fast growing cells [ 112 , 113 ]. Contrary to our results, BaP has been found to induce apoptosis in several cells including neurons and hepatocytes [ 114 , 115 , 116 , 117 ].…”

Section: Discussioncontrasting

confidence: 99%

Chemoresistance to Cancer Treatment: Benzo-α-Pyrene as Friend or Foe?

et al. 2018

View full text Add to dashboard Cite

Background: Environmental pollution such as exposure to pro-carcinogens including benzo-α-pyrene is becoming a major problem globally. Moreover, the effects of benzo-α-pyrene (BaP) on drug pharmacokinetics, pharmacodynamics, and drug resistance warrant further investigation, especially in cancer outpatient chemotherapy where exposure to environmental pollutants might occur. Method: We report here on the effects of benzo-α-pyrene on esophageal cancer cells in vitro, alone, or in combination with chemotherapeutic drugs cisplatin, 5-flurouracil, or paclitaxel. As the study endpoints, we employed expression of proteins involved in cell proliferation, drug metabolism, apoptosis, cell cycle analysis, colony formation, migration, and signaling cascades in the WHCO1 esophageal cancer cell line after 24 h of treatment. Results: Benzo-α-pyrene had no significant effect on WHCO1 cancer cell proliferation but reversed the effect of chemotherapeutic drugs by reducing drug-induced cell death and apoptosis by 30–40% compared to drug-treated cells. The three drugs significantly reduced WHCO1 cell migration by 40–50% compared to control and BaP-treated cells. Combined exposure to drugs was associated with significantly increased apoptosis and reduced colony formation. Evaluation of survival signaling cascades showed that although the MEK-ERK and Akt pathways were activated in the presence of drugs, BaP was a stronger activator of the MEK-ERK and Akt pathways than the drugs. Conclusion: The present study suggest that BaP can reverse the effects of drugs on cancer cells via the activation of survival signaling pathways and upregulation of anti-apoptotic proteins such as Bcl-2 and Bcl-xL. Our data show that BaP contribute to the development of chemoresistant cancer cells.

show abstract

Section: Discussioncontrasting

confidence: 99%

Chemoresistance to Cancer Treatment: Benzo-α-Pyrene as Friend or Foe?

et al. 2018

View full text Add to dashboard Cite

show abstract

“…B(a)P induces apoptosis in testicular cells ( Jiang et al, 2013 ; Das et al, 2014 ; Michurina et al, 2014 ; Nie et al, 2014 ). Reports from our laboratory have shown that B(a)P induced apoptosis in testis ( Banerjee et al, 2016 ).…”

Section: Resultsmentioning

confidence: 99%

Benzo(a)pyrene Induced p53 Mediated Male Germ Cell Apoptosis: Synergistic Protective Effects of Curcumin and Resveratrol

et al. 2016

View full text Add to dashboard Cite

Benzo(a)pyrene (B(a)P) is an environmental toxicant that induces male germ cell apoptosis. Curcumin and resveratrol are phytochemicals with cytoprotective and anti-oxidative properties. At the same time resveratrol is also a natural Aryl hydrocarbon Receptor (AhR) antagonist. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted the synergistic protective effect of curcumin and resveratrol against B(a)P induced p53 mediated germ cell apoptosis. Curcumin-resveratrol significantly prevented B(a)P induced decrease in sperm cell count and motility, as well as increased serum testosterone level. Curcumin-resveratrol co-treatment actively protected B(a)P induced testicular germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3, 8 and 9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, and Apaf1. B(a)P induced testicular reactive oxygen species (ROS) generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 (Cytochrome P4501A1) expression. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.

show abstract

“…Kim showed that BaP-induced apoptosis in RL95-2 cells is accompanied by the activation of caspase (Kim et al, 2007). Nie provided direct evidence that BaP induces apoptotic death of cerebral neurons (Nie et al, 2014).…”

Section: Discussionmentioning

confidence: 97%

“…In addition, the Al concentration is reportedly increased in the brains of AD patients (Andrási et al, 2005;Walton, 2009;Rusina et al, 2011;Bhattacharjee et al, 2013). BaP was reported to induce neurobehavioral deficits in both coking plant workers (Niu et al, 2010) and rats (Nie et al, 2013), and BaP-induced neurotoxicity is involved in the mechanism of neuron apoptosis (Nie et al, 2014). Because both BaP and Al are neurotoxic and humans are often co-exposed to both chemicals, these chemicals are likely to synergistically damage the central nervous system to exacerbate human health problems.…”

Section: Discussionmentioning

confidence: 99%

Aluminum and benzo[a]pyrene co-operate to induce neuronal apoptosis <i>in vitro </i>

et al. 2015

View full text Add to dashboard Cite

Toxic and harmful factors co-exist in the environment; these factors often interact to induce combined toxicity, which is the main focus of toxicological research. Furthermore, a large number of studies have shown that aluminum (Al) and benzo[a]pyrene (BaP) are neurotoxic and target the central nervous system to cause neuronal apoptosis. Because we are exposed to both Al and BaP in the air, water, food, and even medicine, the combined effects of these agents in humans must be examined. The present study examines the ability of Al and BaP co-exposure to intensify neuronal apoptosis. The primary neurons of newborn rats were cultured for 5 days, and cells from the same batch that were growing well were selected and assigned to the blank control group, the solvent control group (DMSO+S9+maltol), BaP groups (10, 40 μmol/L), Al (mal)3 groups (50, 100, 400 μmol/L) and co-exposure groups with different combinations of BaP and Al (mal)3. The cell viabilities indicated that 10 μM BaP or 50 μM Al (mal)3 was mildly toxic, and we selected 10 μM BaP+50 μM Al (mal)3 for subsequent co-exposure experiments. The morphological characteristics of cell apoptosis were much more obvious in the co-exposure group than in the Al-exposed cells or the BaP-exposed cells, as observed with a transmission electron microscope and a fluorescence inverted microscope. The apoptotic rates and caspase-3 activity quantitatively significantly differed between the co-exposure and Al-exposure groups, while the BaP-exposure group did not significantly differ from the control group. These results indicate that Al and BaP co-exposure exert synergistic effects on neuronal cell apoptosis.

show abstract

Involvement of mitochondrial pathway in benzo[a]pyrene-induced neuron apoptosis

Cited by 24 publications

References 43 publications

Chemoresistance to Cancer Treatment: Benzo-α-Pyrene as Friend or Foe?

Chemoresistance to Cancer Treatment: Benzo-α-Pyrene as Friend or Foe?

Benzo(a)pyrene Induced p53 Mediated Male Germ Cell Apoptosis: Synergistic Protective Effects of Curcumin and Resveratrol

Aluminum and benzo[a]pyrene co-operate to induce neuronal apoptosis <i>in vitro </i>

Contact Info

Product

Resources

About