Evidence map›Paper›PMID 34510030›Full record

ArticleAging2021

Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cells.

Yan Zhang, Ning He, Xuejian Zhou, Feifan Wang, Hairong Cai, Shih Han Huang, Xianwu Chen, Zhenghui Hu, Xiaodong Jin

Open access · hybridAbstract read
In one paragraph

Article in Aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

24 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Article
  3. Betulinic acid isolated fromHistology and histopathology · 2026
    Article
  4. The Role of Natural Compounds in Bladder Urothelial Carcinoma Treatment.International journal of molecular sciences · 2026
    Review
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  6. Article
  7. Article
  8. Article
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  10. Article
  11. Review
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  14. Article
  15. HomogeneousPharmaceutical biology · 2024
    Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. 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

9 authors at 2 institutions in 1 country.

Yan ZhangDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, P.R. China.
Ning HeDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, P.R. China.
Xuejian ZhouDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, P.R. China.
Feifan WangDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, P.R. China.
Hairong CaiDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, P.R. China.
Shih Han HuangDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, P.R. China.
Xianwu ChenDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, P.R. China.
Zhenghui HuDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, P.R. China.
Xiaodong JinDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang, P.R. China.
Zhejiang University · CNFirst Affiliated Hospital Zhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Betulinic acid (BA), a pentacyclic triterpenoid isolated from tree bark, exhibits antitumor effects against solid malignancies and triggers autophagy and/or apoptosis in human cancer cells. Nonetheless, the relationship between autophagy and apoptosis and the potential modulatory actions of BA on autophagy-dependent bladder cancer cell death remain unclear. The present study showed that BA exposure significantly suppressed viability, proliferation, and migration of EJ and T24 human bladder cancer cells. These effects reflected caspase 3-mediated apoptosis and could be attenuated or abolished by inhibiting ROS production with N-acetyl-L-cysteine, inhibiting autophagy with chloroquine, or silencing ATG7 with targeted siRNA. BA-induced autophagy was evidenced by epifluorescence imaging of lentivirus-induced expression of mCherry-GFP-LC3B and increased expression of two autophagy-related proteins, LC3B-II and TEM. Moreover, enhanced AMPK phosphorylation and decreased mTOR and ULK-1 phosphorylation suggested BA activates autophagy via the AMPK/mTOR/ULK1 pathway. Accordingly, exposure to dorsomorphin (Compound C), an AMPK inhibitor, and AICAR, an AMPK activator, respectively inhibited and stimulated BA-induced autophagy in EJ and T24 cells. The effects of Bmi-1 overexpression

Indexed as

AnimalsApoptosisAutophagyAutophagy-Related Protein-1 HomologBetulinic AcidCell Line, TumorCell MovementCell ProliferationCell SurvivalGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsMiceMice, NudeMitogen-Activated Protein Kinase 7Pentacyclic TriterpenesAutophagy-Related Protein-1 HomologBetulinic AciddorsomorphinIntracellular Signaling Peptides and ProteinsMAPK7 protein, humanMitogen-Activated Protein Kinase 7Pentacyclic TriterpenesProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsPyrazolesPyrimidinesROS1 protein, humanTOR Serine-Threonine KinasesULK1 protein, humanAMPK pathwayapoptosisautophagybetulinic acidbladder cancer

Identifiers

PMID34510030
PMCPMC8457576
OpenAlexW3200858447

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.