背景:生育三烯酚,一种维生素E,以其抗癌和其他生物活性而闻名。本系统综述旨在总结内质网应激(ERS)和随后的未折叠蛋白反应(UPR)作为生育三烯酚抗癌特性的潜在分子机制的参与。
方法:2023年3月使用PubMed进行了全面的文献检索,Scopus,WebofScience,EMBASE数据库。体外,在体内,并考虑了人类研究。
结果:在最初的检索过程中,共检索到840篇文章,纳入11篇符合入选标准的文章进行定性分析.目前的机理发现仅基于体外研究。生育三烯酚诱导癌细胞生长停滞,自噬,和细胞死亡主要通过细胞凋亡,但也通过类似凋亡的细胞死亡。富含生育三烯酚的馏分,包括α-,γ-和δ-生育三烯酚,诱发ERS,UPR标志物和/或ERS相关凋亡标志物的上调证明了这一点。早期内质网钙离子释放,神经酰胺水平升高,蛋白酶体抑制,和microRNA-190b的上调被认为是调节生育三烯酚介导的ERS/UPR转导所必需的。然而,生育三烯酚诱导ERS的上游分子机制尚不清楚.
结论:ERS和UPR在调节生育三烯酚介导的抗癌作用中至关重要。需要进一步的研究来阐明生育三烯酚介导的ERS的上游分子机制。
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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.