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

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.

Computational Evaluation of the Potential of Salicylate Compound from Syzygium aromaticum on Carbonic Anhydrase I as a Gastric Acid Stimulant

“…However, it is important to note that there are many other factors to consider before a compound can be deemed a potential drug, including side effects and production costs. [34][35][36] The results of this study provide strong evidence for the potential of salicylate compound (Syzygium Aromaticum) in stimulating Carbonic Anhydrase I, an enzyme crucial in gastric acid regulation. The high Binding Affinity values (-7.3, -7.3, -6.5) indicate that salicylate has a strong affinity for Carbonic Anhydrase I, suggesting that the compound can efficiently interact with the enzyme.…”

Hepatitis E Inhibited by Rosmarinic Acid Extract from Clove Plant (Syzygium Aromaricum) through Computational Analysis

“…Thus, this research provides a new contribution to the development of therapies for this disease. 41,42 Furthermore, this research has the uniqueness of specifically focusing on Hepatitis E and the potential of Rosmarinic Acid as an inhibitor.…”

In Silico Study on the Potential of Guaiacol Extract from Green Tea (Camellia sinensis) as a Stimulant for Carbanoic Anhydrase II in Renal Tubular Acidosis

“…This interpretation directly highlights the potential role of Guaiacol as a drug in addressing metabolic disorders associated with renal tubular acidosis. 33,34 Furthermore, the analysis of RMSD results depicts the stability level of the Guaiacol-CA II complex. The stability resulting from the interaction between Guaiacol and CA II is a key factor in determining the success of a drug in stimulating enzyme activity.…”