Evidence map›Paper›PMID 27626481›Full record

ArticleOncotarget2016

Zanthoxylum fruit extract from Japanese pepper promotes autophagic cell death in cancer cells.

Reo Nozaki, Toru Kono, Hiroki Bochimoto, Tsuyoshi Watanabe, Kaori Oketani, Yuichi Sakamaki, Naoto Okubo, Koji Nakagawa, Hiroshi Takeda

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

11 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Antitumor components and mechanisms ofFrontiers in pharmacology · 2025
    Review
  3. Dietary Replacement of Soybean Meal withAnimals : an open access journal from MDPI · 2024
    Article
  4. Hydroxy-γ-sanshool fromFrontiers in nutrition · 2022
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Medicinal Plants in the Prevention and Treatment of Colon Cancer.Oxidative medicine and cellular longevity · 2019
    Review
  10. Article
  11. 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 3 institutions in 1 country.

Reo NozakiPathophysiology and Therapeutics, Hokkaido University Faculty of Pharmaceutical Sciences, Sapporo, Hokkaido, Japan.
Toru KonoPathophysiology and Therapeutics, Hokkaido University Faculty of Pharmaceutical Sciences, Sapporo, Hokkaido, Japan.
Hiroki BochimotoDepartment of Microscopic Anatomy and Cell Biology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
Tsuyoshi WatanabeDepartment of Microscopic Anatomy and Cell Biology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
Kaori OketaniPathophysiology and Therapeutics, Hokkaido University Faculty of Pharmaceutical Sciences, Sapporo, Hokkaido, Japan.
Yuichi SakamakiPathophysiology and Therapeutics, Hokkaido University Faculty of Pharmaceutical Sciences, Sapporo, Hokkaido, Japan.
Naoto OkuboPathophysiology and Therapeutics, Hokkaido University Faculty of Pharmaceutical Sciences, Sapporo, Hokkaido, Japan.
Koji NakagawaPathophysiology and Therapeutics, Hokkaido University Faculty of Pharmaceutical Sciences, Sapporo, Hokkaido, Japan.
Hiroshi TakedaPathophysiology and Therapeutics, Hokkaido University Faculty of Pharmaceutical Sciences, Sapporo, Hokkaido, Japan.
Hokkaido Pharmaceutical University · JPHokkaido University · JPAsahikawa Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Zanthoxylum fruit, obtained from the Japanese pepper plant (Zanthoxylum piperitum De Candolle), and its extract (Zanthoxylum fruit extract, ZFE) have multiple physiological activities (e.g., antiviral activity). However, the potential anticancer activity of ZFE has not been fully examined. In this study, we investigated the ability of ZFE to induce autophagic cell death (ACD). ZFE caused remarkable autophagy-like cytoplasmic vacuolization, inhibited cell proliferation, and ultimately induced cell death in the human cancer cell lines DLD-1, HepG2, and Caco-2, but not in A549, MCF-7, or WiDr cells. ZFE increased the level of LC3-II protein, a marker of autophagy. Knockdown of ATG5 using siRNA inhibited ZFE-induced cytoplasmic vacuolization and cell death. Moreover, in cancer cells that could be induced to undergo cell death by ZFE, the extract increased the phosphorylation of c-Jun N-terminal kinase (JNK), and the JNK inhibitor SP600125 attenuated both vacuolization and cell death. Based on morphology and expression of marker proteins, ZFE-induced cell death was neither apoptosis nor necrosis. Normal intestinal cells were not affected by ZFE. Taken together, our findings show that ZFE induces JNK-dependent ACD, which appears to be the main mechanism underlying its anticancer activity, suggesting a promising starting point for anticancer drug development.

Indexed as

A549 CellsAnimalsAnthracenesAutophagyAutophagy-Related Protein 5Caco-2 CellsCell DeathCell LineCell Line, TumorCell ProliferationFruitHep G2 CellsHumansJNK Mitogen-Activated Protein KinasesMCF-7 CellsPhosphorylationAnthracenesATG5 protein, humanAutophagy-Related Protein 5JNK Mitogen-Activated Protein KinasesPlant Extractspyrazolanthroneautophagic cell deathautophagycolon cancervacuolizationzanthoxylum fruit

Identifiers

PMID27626481
PMCPMC5342563
OpenAlexW2515155556

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.