Abstract：
Autophagy and endoplasmic reticulum (ER) stress are conserved processes that generally promote survival, but can induce cell death when physiological thresholds are crossed. The pro-survival aspects of these processes are exploited by cancer cells for tumor development and progression. Therefore, anticancer drugs targeting autophagy or ER stress to induce cell death and/or block the pro-survival aspects are being investigated extensively. Consistently, several phytochemicals have been reported to exert their anticancer effects by modulating autophagy and/or ER stress. Various phytochemicals (e.g., celastrol, curcumin, emodin, resveratrol, among others) activate the unfolded protein response to induce ER stress-mediated apoptosis through different pathways. Similarly, various phytochemicals induce autophagy through different mechanisms (namely mechanistic target of Rapamycin [mTOR] inhibition). However, phytochemical-induced autophagy can function either as a cytoprotective mechanism or as programmed cell death type II. Interestingly, at times, the same phytochemical (e.g., 6-gingerol, emodin, shikonin, among others) can induce cytoprotective autophagy or programmed cell death type II depending on cellular contexts, such as cancer type. Although there is well-documented mechanistic interplay between autophagy and ER stress, only a one-way modulation was noted with some phytochemicals (carnosol, capsaicin, cryptotanshinone, guangsangon E, kaempferol, and δ-tocotrienol): ER stress-dependent autophagy. Plant extracts are sources of potent phytochemicals and while numerous phytochemicals have been investigated in preclinical and clinical studies, the search for novel phytochemicals with anticancer effects is ongoing from plant extracts used in traditional medicine (e.g., Origanum majorana). Nonetheless, the clinical translation of phytochemicals, a promising avenue for cancer therapeutics, is hindered by several limitations that need to be addressed in future studies.
摘要：
自噬和内质网（ER）应激是通常促进生存的保守过程，但是当生理阈值交叉时可以诱导细胞死亡。这些过程的促存活方面被癌细胞用于肿瘤发展和进展。因此,靶向自噬或ER应激诱导细胞死亡和/或阻断促存活方面的抗癌药物正在被广泛研究.始终如一，已经报道了几种植物化学物质通过调节自噬和/或内质网应激发挥其抗癌作用。各种植物化学物质(例如，celastrol,姜黄素,大黄素,白藜芦醇,除其他外）激活未折叠的蛋白质反应，以通过不同途径诱导ER应激介导的凋亡。同样，各种植物化学物质通过不同的机制(即雷帕霉素[mTOR]抑制的机制靶点)诱导自噬。然而,植物化学诱导的自噬既可以作为细胞保护机制，也可以作为II型程序性细胞死亡。有趣的是,有时,相同的植物化学物质(例如，6-姜辣素,大黄素,紫草,除其他外）可以根据细胞环境诱导细胞保护自噬或II型程序性细胞死亡，如癌症类型。尽管自噬和内质网应激之间存在有据可查的机制相互作用，一些植物化学物质只注意到单向调制(鼠尾草，辣椒素,cryptotanshinone,广生E,山奈酚,和δ-生育三烯酚）：ER应激依赖性自噬。植物提取物是有效的植物化学物质的来源，虽然许多植物化学物质已经在临床前和临床研究中进行了研究，正在从传统医学中使用的植物提取物中寻找具有抗癌作用的新型植物化学物质(例如，Origanummajorana).尽管如此，植物化学物质的临床翻译，癌症治疗的一个有希望的途径，受到一些限制的阻碍，需要在未来的研究中解决。
