Trifluoperazine Synergistically Potentiates Bortezomib-Induced Anti-Cancer Effect in Multiple Myeloma via Inhibiting P38 MAPK/NUPR1

Jing, Zizi; Yu, Wei; Li, Anmao; Chen, Xuanxin; Chen, Yuying; Chen, Jianbin

doi:10.1620/tjem.2022.j044

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…The present study aimed to identify the underlying mechanism of TFP-induced intracellular Ca 2+ increase and cell death in glioma cells. Previous reports have demonstrated that TFP has anti-cancer activity on several cancers including glioma (10)(11)(12)(22)(23)(24)(25). However, to the best of our knowledge, there is no report on how TFP induces cancer cell death, especially in glioma.…”

Section: Discussionmentioning

confidence: 92%

COX-2 Acts as a Key Mediator of Trifluoperazine-induced Cell Death in U87MG Glioma Cells

2022

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Background/Aim: Glioblastoma multiforme (GBM) is one of the most common brain tumors with a poor prognosis. Previously, we reported that trifluoperazine (TFP), a wellknown antipsychotic, has anti-glioma activity through the modulation of intracellular calcium levels. The present study aimed to investigate the anti-cancer mechanism of action of TFP on glioma cells. Materials and Methods: The effect of TFP on U87MG cells was examined using a viability assay, flow cytometry, enzyme-linked immunosorbent assay, quantitative real-time PCR, western blot analysis, colony formation, and immunocytochemistry. Results: TFP treatment decreased cell viability. To test the possible involvement of COX-2 in the anticancer activity of TFP on U87MG cells, a COX-2 inhibitor was applied. COX-2 inhibitor pretreatment restored TFP-induced reduction in viability to the control level. Additionally, TFPinduced changes in the apoptotic cell population, production of prostaglandins (PGE 2 , PGD 2 , 15d-PGJ 2 ), and nuclear translocation of peroxisome proliferator-activated receptor γ (PPARγ) were ameliorated by COX-2 inhibitor pretreatment. Conclusion: TFP suppressed the proliferation of U87MG glioma cell in a COX-2/PPARγ-dependent manner.Glioblastoma multiforme (GBM) is a malignant brain tumor derived from glial cells. The prognosis of patients is very low. Median survival is less than 10 months. GBM treatment usually Materials and MethodsCell culture. U87MG, U251MG, and T98G cells were purchased from the American Type Culture Collection and cultured in Dulbecco's Modified Eagle's Medium supplemented with 10% fetal 5773 *These Authors contributed equally to this study.

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Section: Discussionmentioning

confidence: 92%

COX-2 Acts as a Key Mediator of Trifluoperazine-induced Cell Death in U87MG Glioma Cells

2022

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“…Through prediction and experimental verification, NUPR1 was found to be one of the target genes of miR-4443, as was already shown in a previous study [ 50 ], and this affects the proliferation, migration, and invasion of osteosarcoma cells [ 51 ]. p38 MAPK has been shown to induce the expression of NUPR1 in astrocytes and pancreatic cancer cells [ 52 ], and silencing of NUPR1 reduces the expression level of p38 MAPK [ 53 ], suggesting that NUPR1 interacts with the MAPK pathway. Our study showed that miR-4443 regulated the expression of NUPR1, thereby possibly affecting the MAPK pathway and the replication of EV71.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA ENST00000469812 promotes Enterovirus type 71 replication via targeting the miR-4443/NUPR1 axis in rhabdomyosarcoma cells

Long

Gao

et al. 2022

Arch Virol

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Hand, foot, and mouth disease (HFMD) caused by Enterovirus type 71 (EV71) is a serious threat to children’s health. However, the pathogenic mechanism of EV71 is still unclear. Long non-coding RNAs (lncRNAs), some of which bind to miRNA as competitive endogenous RNAs (ceRNA) and weaken the silencing effect on the mRNA of downstream target genes, play a key role in regulating the viral infection process. In this study, through experimental verification, we found miR-4443 to be downregulated in cells infected with EV71. Next, by predicting lncRNAs that potentially regulate miR-4443, we found that EV71 infection induced upregulation of lncRNA ENST00000469812 and then further downregulated miR-4443 expression by direct interaction. We also demonstrated that nuclear protein 1 (NUPR1) is one of the target genes of miR-4443 and is involved in the ENST00000469812/miR-4443/NUPR1 regulatory axis. Finally, the ENST00000469812/miR-4443/NUPR1 regulatory axis exhibited a positive effect on EV71 replication. Here, we lay a foundation for exploring the pathogenic mechanism of EV71 and identify potential targets for HFMD treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s00705-022-05596-3

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“…p38 is constitutively activated in MM and has been implicated in osteoclast and osteoblast activity and bone destruction [11]. Recent studies have shown that treatment with bortezomib can induce p38 activation, and this activation may be related to chemoresistance [12,13]. However, other studies show that p38 activation is associated with the induction of apoptosis and autophagy in MM [14].…”

Section: Introductionmentioning

confidence: 99%

p38 Molecular Targeting for Next-Generation Multiple Myeloma Therapy

Morales-Martínez,

Vega

2024

Cancers

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Resistance to therapy and disease progression are the main causes of mortality in most cancers. In particular, the development of resistance is an important limitation affecting the efficacy of therapeutic alternatives for cancer, including chemotherapy, radiotherapy, and immunotherapy. Signaling pathways are largely responsible for the mechanisms of resistance to cancer treatment and progression, and multiple myeloma is no exception. p38 mitogen-activated protein kinase (p38) is downstream of several signaling pathways specific to treatment resistance and progression. Therefore, in recent years, developing therapeutic alternatives directed at p38 has been of great interest, in order to reverse chemotherapy resistance and prevent progression. In this review, we discuss recent findings on the role of p38, including recent advances in our understanding of its expression and activity as well as its isoforms, and its possible clinical role based on the mechanisms of resistance and progression in multiple myeloma.

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Trifluoperazine Synergistically Potentiates Bortezomib-Induced Anti-Cancer Effect in Multiple Myeloma via Inhibiting P38 MAPK/NUPR1

Cited by 5 publications

References 38 publications

COX-2 Acts as a Key Mediator of Trifluoperazine-induced Cell Death in U87MG Glioma Cells

COX-2 Acts as a Key Mediator of Trifluoperazine-induced Cell Death in U87MG Glioma Cells

Long non-coding RNA ENST00000469812 promotes Enterovirus type 71 replication via targeting the miR-4443/NUPR1 axis in rhabdomyosarcoma cells

p38 Molecular Targeting for Next-Generation Multiple Myeloma Therapy

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