Di-Ethylhexylphthalate (DEHP) Modulates Cell Invasion, Migration and Anchorage Independent Growth through Targeting S100P in LN-229 Glioblastoma Cells

Sims, Jennifer N.; Graham, Barbara; Pacurari, Maricica; Leggett, S.; Tchounwou, Paul B.; Ndebele, Kenneth

doi:10.3390/ijerph110505006

Cited by 18 publications

(15 citation statements)

References 20 publications

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“…Cell cycle progression is regulated mainly by the tumor suppressor protein (pRb) and transcriptional factor (E2F1) simultaneously. pRb is phosphorylated by nearly 16 residues prominently S608 and T373 by CDKs leading to heteromerization with E2F1 and regulated cancer cells proliferation 8,9,11–14,17–25,38 . ATO has been used successfully for treatment of APL patients by inhibiting APL cells proliferation at higher concentrations 4,39 .…”

Section: Discussionmentioning

confidence: 99%

Arsenic trioxide reduces the expression of E2F1, cyclin E, and phosphorylation of PI3K signaling molecules in acute leukemia cells

Kumar

Tchounwou

2021

Environmental Toxicology

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Arsenic trioxide (ATO) has been used for the treatment of acute promyelocytic leukemia (APL). Although ATO modulates cell cycle progression and apoptosis in APL cells, its exact mechanism of action remains elusive. In this research, we investigated its effects on E2F1, cyclin E, p53, pRb, and PI3K signaling molecules by western blotting, immunocytochemistry and/or confocal imaging. We found that ATO inhibited the proliferation of APL cells through down‐regulation of E2F1 and cyclin E expression, and stimulation of pRb. It also reduced the interaction of pRb and E2F1with binding to the E2F1 promoter, by stimulating pRb association. ATO also effected the phosphorylation of pRb at S608 and T373 residues and association of E2F1, pRb, and p53, simultaneously. However, in p53‐knockdown NB4 cells, ATO did not significantly reduce E2F1 and cyclin E expression. Our findings demonstrate that ATO inhibits APL cell growth through reduced expression of E2F1, cyclin E, and stimulation of pRb. It also effected both interaction and association of E2F1, pRb, and p53 by phosphorylation of pRb at T373 and S608 residues and reduced phosphorylation of PI3K signaling molecules. This novel mode of action of ATO in APL cells may be useful for designing new APL drugs.

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Section: Discussionmentioning

confidence: 99%

Arsenic trioxide reduces the expression of E2F1, cyclin E, and phosphorylation of PI3K signaling molecules in acute leukemia cells

Kumar

Tchounwou

2021

Environmental Toxicology

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“…We made p53 knockdown NB4 cells using lentivirus shRNA (Dharmacon Inc; Lafayette, CO) method as described earlier [ 55 ]. In brief, we seeded 10,000 NB4 cells in 25 µl of transduction medium (RPMI 1640) without serum in each well with polybrene (8 µg/ml).…”

Section: Methodsmentioning

confidence: 99%

Trisenox disrupts MDM2-DAXX-HAUSP complex and activates p53, cell cycle regulation and apoptosis in acute leukemia cells

2018

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Trisenox (TX) has been used in the treatment of both de novo and relapsed acute promyelocytic leukemia (APL) patients. Using in vitro APL cell lines model in this research, we report on a new target of TX action through disruption of MDM2-DAXX-HAUSP complex, degradation of MDM2, and activation of p53 expression. TX–induced stress signal was transmitted by protein kinase (ATM & ATR) and phosphorylation of its downstream targets CHK1, CHK2, ATM, and ATR, respectively at the Ser 345, Thr68, Ser1981 and Ser 428 residues involved in complex disruption and p53 up-regulation. TX-activated p53 led to cell cycle arrest and apoptosis in APL cells. Our results showed that TX inhibited cell proliferation, disrupted complex molecules expression and association in APL cells. Our functional studies indicated that TX-induced down-regulation of complex molecules expression was mostly neutralized in both p53 knockdown NB4 cells and nutilin-3 treated KG1a cells. Hence our findings provide a functional evidence of TX action on cell cycle regulation and apoptosis in APL cells. This novel target of TX activity may be useful for designing new APL drugs.

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“…6a). The studies showed that miR-148a-regulated proteins, such as GADD45A, GRP78, PARK7, and S100P, are invovled in cell-cell adhesion and are associated with the formation and invasion of glioma [25][26][27][28]. In addition, miR-148a also regulates other important biological processes, including apoptosis, DNA repair, mitosis cycle regulation, cell proliferation, nucleosome assembly, nucleocytoplasmic transport, and translational initiation, and these are related to the occurrence and development of cancer.…”

Section: Functional Enrichment Of Mir-148a-regulated Proteinsmentioning

confidence: 99%

The role of microRNA-148a and downstream DLGAP1 on the molecular regulation and tumor progression on human glioblastoma

Zeng

et al. 2019

Oncogene

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Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Currently, the prognosis of the patients with GBM is very poor and new molecular targets and treatment strategies are urgently needed to combat it. MicroRNA-148a (miR-148a) has been shown to be dysregulated in certain tumor types. However, the role of miR-148a in the pathogenesis of GBM is not fully understood. Here we comprehensively analyzed the roles of miR-148a, downstream DLGAP1, and their molecular pathways in GBM. We showed that miR-148a promote the proliferation and growth of GBM cells both in vitro and in vivo, and also induced the migration, invasion, and EMT (epithelial-mesenchymal transition) program of GBM cells by directly targeting DLGAP1. Furthermore, we identified 31 new miR-148a targets and found that miR-148a function was mainly involved in the cell adhesion signaling pathway and was associated with nervous system diseases. Our findings provide a new mechanism for miR-148a-mediated GBM cell invasion and reveal previously unreported targets of miR-148a as well as novel miR-148a-mediated regulatory networks in GBM. These results increase the understanding of the role of miR-148a in GBM and may lead to novel therapeutic strategies for GBM.

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Di-Ethylhexylphthalate (DEHP) Modulates Cell Invasion, Migration and Anchorage Independent Growth through Targeting S100P in LN-229 Glioblastoma Cells

Cited by 18 publications

References 20 publications

Arsenic trioxide reduces the expression of E2F1, cyclin E, and phosphorylation of PI3K signaling molecules in acute leukemia cells

Arsenic trioxide reduces the expression of E2F1, cyclin E, and phosphorylation of PI3K signaling molecules in acute leukemia cells

Trisenox disrupts MDM2-DAXX-HAUSP complex and activates p53, cell cycle regulation and apoptosis in acute leukemia cells

The role of microRNA-148a and downstream DLGAP1 on the molecular regulation and tumor progression on human glioblastoma

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