Evidence map›Paper›PMID 30760707›Full record

ArticleCell death & disease2019

Fisetin induces autophagy in pancreatic cancer cells via endoplasmic reticulum stress- and mitochondrial stress-dependent pathways.

Shengnan Jia, Xiaodong Xu, Senhao Zhou, Yan Chen, Guoping Ding, Liping Cao

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 90 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 2 pooled it
10.5field-weighted citation impact, top 1% 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

90 citing papers in PubMed, 2 syntheses or guidelines pooled it, 159 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Fisetin alleviates pulmonary arterial hypertension by inhibiting the TGF-β1/Smad 2/3 signaling pathway.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026
    Article
  5. Article
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  7. Article
  8. Restricting intracellularAutophagy · 2026
    Article
  9. Review
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  14. Article
  15. Article
  16. Senotherapy for chronic lung disease.Pharmacological reviews · 2025
    Review
  17. Article
  18. Article
  19. Review
  20. Review

30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Shengnan JiaDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 310000, Hangzhou, Zhejiang, China.
Xiaodong XuDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 310000, Hangzhou, Zhejiang, China.
Senhao ZhouDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 310000, Hangzhou, Zhejiang, China.
Yan ChenDepartment of General Surgery, Huzhou Hospital, Zhejiang University School of Medicine, 313003, Huzhou, Zhejiang, China.
Guoping DingDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 310000, Hangzhou, Zhejiang, China. dinguop@zju.edu.cn.
Liping CaoDepartment of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 310000, Hangzhou, Zhejiang, China. caolipingzju@zju.edu.cn.
Zhejiang University · CNHuzhou University · CNSir Run Run Shaw Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic cancer is one of the most aggressive tumors and patients have poor survival rates. Fisetin, a natural flavonoid, was recently reported to have antitumor effects in various cancer models. Autophagy is a conserved catabolic process that maintains cellular homoeostasis in response to stress, and together with apoptosis, determines cell fate. Herein, we examined the effect of fisetin on pancreatic cancer. We reveal that fisetin inhibits PANC-1 cell proliferation using a real-time cell analysis system. Moreover, the in vivo antitumor effect of fisetin was verified in pancreatic cancer using a luciferase-expressing murine xenograft pancreatic cancer model. We found that the AMPK/mTOR signaling pathway was enhanced after fisetin treatment; however, autophagy was not diminished by adding the AMPK inhibitor compound C. Thus, we hypothesized that an another autophagy regulating pathway existed. RNA-seq analysis revealed that the unfolded protein response pathway, which is activated by ER stress, was enriched. We also found that the stress-induced transcription factor p8 was increased in fisetin-treated PANC-1 cells, and that fisetin-induced autophagy was blocked by silencing p8. We revealed that p8-dependent autophagy was AMPK-independent, and that p8 regulated ATF6, ATF4, and PERK in response to ER stress via p53/PKC-α-mediated signaling. Furthermore, mitophagy was associated with Parkin and PINK1 in response to mitochondrial stress. Interestingly, ATF4 and ATF6 were increased in cells treated with fisetin and compound C. Moreover, inhibiting the AMPK/mTOR pathway with compound C may upregulate p8-dependent autophagy. Thus, there may be crosstalk between the AMPK/mTOR and p8-dependent pathways.

Indexed as

AnimalsAutophagyEndoplasmic Reticulum StressFlavonoidsFlavonolsHumansMiceMitochondriaPancreatic NeoplasmsfisetinFlavonoidsFlavonols

Identifiers

PMID30760707
PMCPMC6374379
OpenAlexW2914563881

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.