Shiau Jun-Ping, Chuang Ya-Ting, Cheng Yuan-Bin, Tang Jen-Yang, Hou Ming-Feng, Yen Ching-Yu, Chang Hsueh-Wei
Department of Surgery, Kaohsiung Municipal Siaogang Hospital, Kaohsiung 81267, Taiwan.
Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Antioxidants (Basel). 2022 May 6;11(5):911. doi: 10.3390/antiox11050911.
The critical factors for regulating cancer metabolism are oxidative stress and phosphoinositide-3-kinase/AKT serine-threonine kinase/mechanistic target of the rapamycin kinase (PI3K/AKT/mTOR). However, the metabolic impacts of oxidative stress and PI3K/AKT/mTOR on individual mechanisms such as glycolysis (Warburg effect), pentose phosphate pathway (PPP), fatty acid synthesis, tricarboxylic acid cycle (TCA) cycle, glutaminolysis, and oxidative phosphorylation (OXPHOS) are complicated. Therefore, this review summarizes the individual and interacting functions of oxidative stress and PI3K/AKT/mTOR on metabolism. Moreover, natural products providing oxidative stress and PI3K/AKT/mTOR modulating effects have anticancer potential. Using the example of brown algae-derived fucoidan, the roles of oxidative stress and PI3K/AKT/mTOR were summarized, although their potential functions within diverse metabolisms were rarely investigated. We propose a potential application that fucoidan may regulate oxidative stress and PI3K/AKT/mTOR signaling to modulate their associated metabolic regulations. This review sheds light on understanding the impacts of oxidative stress and PI3K/AKT/mTOR on metabolism and the future direction of metabolism-based cancer therapy of fucoidan.
调节癌症代谢的关键因素是氧化应激和磷酸肌醇-3-激酶/AKT丝氨酸-苏氨酸激酶/雷帕霉素激酶的机制性靶点（PI3K/AKT/mTOR）。然而，氧化应激和PI3K/AKT/mTOR对糖酵解（瓦伯格效应）、磷酸戊糖途径（PPP）、脂肪酸合成、三羧酸循环（TCA）、谷氨酰胺分解和氧化磷酸化（OXPHOS）等个体机制的代谢影响是复杂的。因此，本综述总结了氧化应激和PI3K/AKT/mTOR在代谢方面的个体和相互作用功能。此外，具有氧化应激和PI3K/AKT/mTOR调节作用的天然产物具有抗癌潜力。以褐藻来源的岩藻多糖为例，总结了氧化应激和PI3K/AKT/mTOR的作用，尽管它们在不同代谢中的潜在功能很少被研究。我们提出了一种潜在应用，即岩藻多糖可能调节氧化应激和PI3K/AKT/mTOR信号传导，以调节其相关的代谢调节。本综述有助于理解氧化应激和PI3K/AKT/mTOR对代谢的影响以及岩藻多糖基于代谢的癌症治疗的未来方向。
