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Review
. 2022 Sep 19;11(9):1845.
doi: 10.3390/antiox11091845.

The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products

Jun-Ping Shiau  1 , Ya-Ting Chuang  2 , Jen-Yang Tang  3   4 , Kun-Han Yang  5 , Fang-Rong Chang  5 , Ming-Feng Hou  1   6 , Ching-Yu Yen  7   8 , Hsueh-Wei Chang  6   9
Affiliations
Review

The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products

Jun-Ping Shiau et al. Antioxidants (Basel). .

Abstract

Oxidative stress and AKT serine-threonine kinase (AKT) are responsible for regulating several cell functions of cancer cells. Several natural products modulate both oxidative stress and AKT for anticancer effects. However, the impact of natural product-modulating oxidative stress and AKT on cell functions lacks systemic understanding. Notably, the contribution of regulating cell functions by AKT downstream effectors is not yet well integrated. This review explores the role of oxidative stress and AKT pathway (AKT/AKT effectors) on ten cell functions, including apoptosis, autophagy, endoplasmic reticulum stress, mitochondrial morphogenesis, ferroptosis, necroptosis, DNA damage response, senescence, migration, and cell-cycle progression. The impact of oxidative stress and AKT are connected to these cell functions through cell function mediators. Moreover, the AKT effectors related to cell functions are integrated. Based on this rationale, natural products with the modulating abilities for oxidative stress and AKT pathway exhibit the potential to regulate these cell functions, but some were rarely reported, particularly for AKT effectors. This review sheds light on understanding the roles of oxidative stress and AKT pathway in regulating cell functions, providing future directions for natural products in cancer treatment.

Keywords: AKT signaling; cell function; natural product; oxidative stress.

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Conflict of interest statement

The authors declare that there are no conflict of interest among them.

Figures

Figure 1
Figure 1
Network for oxidative stress and AKT pathway regulations of cell functions in cancer cell treatments. Several AKT effectors are included in this review, such as forkhead box transcription factors (FOXO), c-Myc, hypoxia-inducible factor (HIF), mechanistic target of rapamycin complex 1/2 (mTORC1/2), mTOR substrate S6 kinase 1/2 (S6K1/2), sterol regulatory element-binding protein 1 (SREBP1), and glycogen synthase kinase 3 (GSK3). Several cell functions are included, such as apoptosis, autophagy, ER stress, mitochondrial morphogenesis, ferroptosis, necroptosis, DNA damage response, senescence, migration, and cell-cycle progression.
Figure 2
Figure 2
Hypothesis: Natural products modulating oxidative stress and the AKT pathway (AKT and AKT effectors) regulate several cell functions. The oxidative stress-AKT effector signaling is shown in Figure 1. Detailed future works are warranted to assess additional cell functions that are affected by natural products for anticancer treatment.
See this image and copyright information in PMC

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