Evidence map›Paper›PMID 30719778›Full record

ArticleCell proliferation2019

δ-Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells.

Fabrizio Fontana, Roberta Manuela Moretti, Michela Raimondi, Monica Marzagalli, Giangiacomo Beretta, Patrizia Procacci, Patrizia Sartori, Marina Montagnani Marelli, Patrizia Limonta

Open access · goldAbstract read
In one paragraph

Article in Cell proliferation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% 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

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. International journal of molecular sciences · 2026
    Review
  4. Review
  5. Review
  6. Significance of Vitamins A and E in Cancer Progression and Prevention.International journal of molecular sciences · 2025
    Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review

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

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 1 institution in 1 country.

Fabrizio FontanaDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy.
Roberta Manuela MorettiDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy.
Michela RaimondiDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy.
Monica MarzagalliDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy.
Giangiacomo BerettaDepartment of Environmental Science and Policy, Università degli Studi di Milano, Milano, Italy.
Patrizia ProcacciDepartment of Biomedical Sciences for Health, Università degli Studi di Milano, Milano, Italy.
Patrizia SartoriDepartment of Biomedical Sciences for Health, Università degli Studi di Milano, Milano, Italy.
Marina Montagnani MarelliDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy.
Patrizia LimontaDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy.ORCID https://orcid.org/0000-0001-7028-3008
University of Milan · IT

Funding

Fondazione Banca del Monte di Lombardia, PaviaMIUR Progetto di Eccellenza (Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano)PRIN 2015 2015B7M39T_004
6 · The paper itself

Abstract

objectivesProstate cancer, after the phase of androgen dependence, may progress to the castration-resistant prostate cancer (CRPC) stage, with resistance to standard therapies. Vitamin E-derived tocotrienols (TTs) possess a significant antitumour activity. Here, we evaluated the anti-cancer properties of δ-TT in CRPC cells (PC3 and DU145) and the related mechanisms of action. MATERIALS AND

methodsMTT, Trypan blue and colony formation assays were used to assess cell viability/cell death/cytotoxicity. Western blot, immunofluorescence and MTT analyses were utilized to investigate apoptosis, ER stress and autophagy. Morphological changes were investigated by light and transmission electron microscopy.

resultsWe demonstrated that δ-TT exerts a cytotoxic/proapoptotic activity in CRPC cells. We found that in PC3 cells: (a) δ-TT triggers both the endoplasmic reticulum (ER) stress and autophagy pathways; (b) autophagy induction is related to the ER stress, and this ER stress/autophagy axis is involved in the antitumour activity of δ-TT; in autophagy-defective DU145 cells, only the ER stress pathway is involved in the proapoptotic effects of δ-TT; (c) in both CRPC cell lines, δ-TT also induces an intense vacuolation prevented by the ER stress inhibitor salubrinal and the protein synthesis inhibitor cycloheximide, together with increased levels of phosphorylated JNK and p38, supporting the induction of paraptosis by δ-TT.

conclusionsThese data demonstrate that apoptosis, involving ER stress and autophagy (in autophagy positive PC3 cells), and paraptosis are involved in the anti-cancer activity of δ-TT in CRPC cells.

Indexed as

Antineoplastic AgentsApoptosisAutophagyCell DeathCell Line, TumorEndoplasmic Reticulum StressHumansMaleMicroscopy, Electron, TransmissionPC-3 CellsProstatic Neoplasms, Castration-ResistantVitamin EAntineoplastic Agentstocotrienol, deltaVitamin EapoptosisautophagyER stressparaptosisprostate cancerδ-tocotrienol

Identifiers

PMID30719778
PMCPMC6536411
OpenAlexW2913768244

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.