Evidence map›Paper›PMID 37545052›Full record

ArticleAutophagy2023

Inhibition of autophagy and induction of glioblastoma cell death by NEO214, a perillyl alcohol-rolipram conjugate.

Mengting Ou, Hee-Yeon Cho, Jie Fu, Thu Zan Thein, Weijun Wang, Stephen D Swenson, Radu O Minea, Apostolos Stathopoulos, Axel H Schönthal, Florence M Hofman and 2 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Autophagy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
6.9field-weighted citation impact, top 2% of its field
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

19 citing papers in PubMed, 32 citations in OpenAlex.

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  14. Assessing Autophagy Flux in Glioblastoma Temozolomide Resistant Cells.Methods in molecular biology (Clifton, N.J.) · 2025
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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

12 authors at 3 institutions in 2 countries.

Mengting OuDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Hee-Yeon ChoDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0002-7141-6420
Jie FuDepartment of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Thu Zan TheinDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Weijun WangDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0002-7430-5937
Stephen D SwensonDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0003-1366-1871
Radu O MineaDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0002-0929-6480
Apostolos StathopoulosDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Axel H SchönthalDepartment of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0003-0662-5653
Florence M HofmanDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Liling TangKey Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
Thomas C ChenDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0002-2183-4667
University of Southern California · USAffiliated Hospital of Southwest Medical University · CNChongqing University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma (GBM) is the most aggressive primary brain tumor, exhibiting a high rate of recurrence and poor prognosis. Surgery and chemoradiation with temozolomide (TMZ) represent the standard of care, but, in most cases, the tumor develops resistance to further treatment and the patients succumb to disease. Therefore, there is a great need for the development of well-tolerated, effective drugs that specifically target chemoresistant gliomas. NEO214 was generated by covalently conjugating rolipram, a PDE4 (phosphodiesterase 4) inhibitor, to perillyl alcohol, a naturally occurring monoterpene related to limonene. Our previous studies in preclinical models showed that NEO214 harbors anticancer activity, is able to cross the blood-brain barrier (BBB), and is remarkably well tolerated. In the present study, we investigated its mechanism of action and discovered inhibition of macroautophagy/autophagy as a key component of its anticancer effect in glioblastoma cells. We show that NEO214 prevents autophagy-lysosome fusion, thereby blocking autophagic flux and triggering glioma cell death. This process involves activation of MTOR (mechanistic target of rapamycin kinase) activity, which leads to cytoplasmic accumulation of TFEB (transcription factor EB), a critical regulator of genes involved in the autophagy-lysosomal pathway, and consequently reduced expression of autophagy-lysosome genes. When combined with chloroquine and TMZ, the anticancer impact of NEO214 is further potentiated and unfolds against TMZ-resistant cells as well. Taken together, our findings characterize NEO214 as a novel autophagy inhibitor that could become useful for overcoming chemoresistance in glioblastoma.

Indexed as

GlioblastomaGliomaAutophagyCell DeathChloroquineHumansLysosomesMonoterpenesRolipramSirolimusTemozolomideTOR Serine-Threonine KinasesChloroquineMonoterpenesperillyl alcoholRolipramSirolimusTemozolomideTOR Serine-Threonine Kinasesautophagic fluxchloroquineglioblastomaMTOR complexNEO214transcription factor EB

Identifiers

PMID37545052
PMCPMC10621246
OpenAlexW4385620534

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.