School of Biosciences, Faculty of Science and Engineering, University of Nottingham Malaysia Campus, Jalan Broga, Semenyih 43500, Selangor, Malaysia.
Biotechnology Research Centre, University of Nottingham Malaysia Campus, Jalan Broga, Semenyih 43500, Selangor, Malaysia.
Int J Mol Sci. 2019 Jan 16;20(2):372. doi: 10.3390/ijms20020372.
Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target cancers. Resistance toward cell death and enhancement of cell survival are the common adaptations in cancer due to its infinite proliferative capacity. Existing cancer treatment strategies that target a single molecular pathway or cancer hallmark fail to fully resolve the problem. Hence, multitargeted anticancer agents that can concurrently target cell death and survival pathways are seen as a promising alternative to treat cancer. Tocotrienols, a minor constituent of the vitamin E family that have previously been reported to induce various cell death mechanisms and target several key survival pathways, could be an effective anticancer agent. This review puts forward the potential application of tocotrienols as an anticancer treatment from a perspective of influencing the life or death decision of cancer cells. The cell death mechanisms elicited by tocotrienols, particularly apoptosis and autophagy, are highlighted. The influences of several cell survival signaling pathways in shaping cancer cell death, particularly NF-κB, PI3K/Akt, MAPK, and Wnt, are also reviewed. This review may stimulate further mechanistic researches and foster clinical applications of tocotrienols via rational drug designs.
恶性肿瘤通常源于细胞复杂分子机制中的精细缺陷，为有效靶向癌症提供了复杂的分子基础。由于其无限增殖能力，抵抗细胞死亡和增强细胞存活是癌症的常见适应机制。现有的靶向单一分子途径或癌症特征的癌症治疗策略未能完全解决这个问题。因此，同时靶向细胞死亡和存活途径的多靶点抗癌药物被视为治疗癌症的一种有前途的替代方法。生育三烯酚是维生素 E 家族的一个次要成分，先前已被报道能诱导多种细胞死亡机制，并靶向几个关键的存活途径，可能是一种有效的抗癌药物。从影响癌细胞生死决定的角度出发，本文综述了生育三烯酚作为抗癌治疗的潜在应用。重点介绍了生育三烯酚引起的细胞死亡机制，特别是细胞凋亡和自噬。还综述了几种细胞存活信号通路对塑造癌细胞死亡的影响，特别是 NF-κB、PI3K/Akt、MAPK 和 Wnt。这篇综述可能会通过合理的药物设计，激发进一步的机制研究和生育三烯酚的临床应用。
