Molecular Mechanism of Tocotrienol-Mediated Anticancer Properties: A Systematic Review of the Involvement of Endoplasmic Reticulum Stress and Unfolded Protein Response

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#humans #tocotrienols #endoplasmic-reticulum-stress #unfolded-protein-response #apoptosis

Molecular Mechanism of Tocotrienol-Mediated Anticancer Properties: A Systematic Review of the Involvement of Endoplasmic Reticulum Stress and Unfolded Protein Response

Pang et al., 2023 | Nutrients | Systematic Review

Citation

Pang Kok-Lun, Mai Chun-Wai, Chin Kok-Yong. Molecular Mechanism of Tocotrienol-Mediated Anticancer Properties: A Systematic Review of the Involvement of Endoplasmic Reticulum Stress and Unfolded Protein Response. Nutrients. 2023-Apr-12;15(8). doi:10.3390/nu15081854

Abstract

BACKGROUND: Tocotrienol, a type of vitamin E, is well known for its anti-cancer and other biological activities. This systematic review aims to summarize the involvement of endoplasmic reticulum stress (ERS) and subsequent unfolded protein response (UPR) as the underlying molecular mechanisms for the anticancer properties of tocotrienol. METHOD: A comprehensive literature search was performed in March 2023 using the PubMed, Scopus, Web of Science, and EMBASE databases. In vitro, in vivo, and human studies were considered. RESULT: A total of 840 articles were retrieved during the initial search, and 11 articles that fit the selection criteria were included for qualitative analysis. The current mechanistic findings are based solely on in vitro studies. Tocotrienol induces cancer cell growth arrest, autophagy, and cell death primarily through apoptosis but also through paraptosis-like cell death. Tocotrienol-rich fractions, including α-, γ- and δ-tocotrienols, induce ERS, as evidenced by upregulation of UPR markers and/or ERS-related apoptosis markers. Early endoplasmic reticulum calcium ion release, increased ceramide level, proteasomal inhibition, and upregulation of microRNA-190b were suggested to be essential in modulating tocotrienol-mediated ERS/UPR transduction. Nevertheless, the upstream molecular mechanism of tocotrienol-induced ERS is largely unknown. CONCLUSION: ERS and UPR are essential in modulating tocotrienol-mediated anti-cancer effects. Further investigation is needed to elucidate the upstream molecular mechanism of tocotrienol-mediated ERS.

Key Findings

ERS and UPR are essential in modulating tocotrienol-mediated anti-cancer effects. Further investigation is needed to elucidate the upstream molecular mechanism of tocotrienol-mediated ERS.

Outcomes Measured

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Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition stress

MeSH Terms

  • Humans
  • Tocotrienols
  • Endoplasmic Reticulum Stress
  • Unfolded Protein Response
  • Apoptosis
  • Cell Death

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Systematic Review, Journal Article
  • Vertical: vitamin-e

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09