Evidence map›Paper›PMID 38717250›Full record

ArticleBioscience reports2024

Temozolomide resistance mechanisms: unveiling the role of translesion DNA polymerase kappa in glioblastoma spheroids in vitro.

Diego Luis Ribeiro, Marcela Teatin Latancia, Izadora de Souza, Abu-Bakr Adetayo Ariwoola, Davi Mendes, Clarissa Ribeiro Reily Rocha, André Van Helvoort Lengert, Carlos Frederico Martins Menck

Abstract read
In one paragraph

Article in Bioscience reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Diego Luis RibeiroDepartament of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.ORCID 0000-0003-1715-966X
Marcela Teatin Latancia *Departament of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
Izadora de SouzaDepartment of Clinical and Experimental Oncology, Federal University of São Paulo, São Paulo, São Paulo, Brazil.
Abu-Bakr Adetayo AriwoolaDepartament of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
Davi MendesDepartament of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
Clarissa Ribeiro Reily RochaDepartment of Clinical and Experimental Oncology, Federal University of São Paulo, São Paulo, São Paulo, Brazil.
André Van Helvoort LengertDepartment of Biophysics, Paulista School of Medicine, Federal University of São Paulo, São Paulo, São Paulo, Brazil.
Carlos Frederico Martins MenckDepartament of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.ORCID 0000-0003-1941-0694

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) #308868/2018-8Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) financial code 001Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) #2019/19435-3 and #2013/08028-1Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) #2020/02836-2Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) #2021/11597-4Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) #2022/03130-1
6 · The paper itself

Abstract

Temozolomide (TMZ) is the leading therapeutic agent for combating Glioblastoma Multiforme (GBM). Nonetheless, the persistence of chemotherapy-resistant GBM cells remains an ongoing challenge, attributed to various factors, including the translesion synthesis (TLS) mechanism. TLS enables tumor cells to endure genomic damage by utilizing specialized DNA polymerases to bypass DNA lesions. Specifically, TLS polymerase Kappa (Polκ) has been implicated in facilitating DNA damage tolerance against TMZ-induced damage, contributing to a worse prognosis in GBM patients. To better understand the roles of Polκ in TMZ resistance, we conducted a comprehensive assessment of the cytotoxic, antiproliferative, antimetastatic, and genotoxic effects of TMZ on GBM (U251MG) wild-type (WTE) and TLS Polκ knockout (KO) cells, cultivated as three-dimensional (3D) tumor spheroids in vitro. Initial results revealed that TMZ: (i) induces reductions in GBM spheroid diameter (10-200 µM); (ii) demonstrates significant cytotoxicity (25-200 μM); (iii) exerts antiproliferative effects (≤25 μM) and promotes cell cycle arrest (G2/M phase) in Polκ KO spheroids when compared with WTE counterparts. Furthermore, Polκ KO spheroids exhibit elevated levels of cell death (Caspase 3/7) and display greater genotoxicity (53BP1) than WTE following TMZ exposure. Concerning antimetastatic effects, TMZ impedes invadopodia (3D invasion) more effectively in Polκ KO than in WTE spheroids. Collectively, the results suggest that TLS Polκ plays a vital role in the survival, cell death, genotoxicity, and metastatic potential of GBM spheroids in vitro when subjected to TMZ treatment. While the precise mechanisms underpinning this resistance remain elusive, TLS Polκ emerges as a potential therapeutic target for GBM patients.

Indexed as

DNA-Directed DNA PolymeraseDrug Resistance, NeoplasmGlioblastomaSpheroids, CellularTemozolomideAntineoplastic Agents, AlkylatingApoptosisBrain NeoplasmsCell Line, TumorCell ProliferationDNA DamageHumansY-Family DNA PolymerasesAntineoplastic Agents, AlkylatingDNA-Directed DNA PolymerasePOLK protein, humanTemozolomideY-Family DNA Polymerases3D spheroidsapoptosisGenotoxicityGliomaTemozolomideTranslesion Synthesis

Identifiers

PMID38717250
PMCPMC11139666

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.