Abstract
Oxidative stress and the AKT serine/threonine kinase (AKT) signaling pathway are essential regulators in cellular migration, metastasis, and angiogenesis. More than 300 withanolides were discovered from the plant family Solanaceae, exhibiting diverse functions. Notably, the relationship between oxidative stress, AKT signaling, and angiogenesis in withanolide treatments lacks comprehensive understanding. Here, we summarize connecting evidence related to oxidative stress, AKT signaling, and angiogenesis in the zebrafish model. A convenient vertebrate model monitored the in vivo effects of developmental and tumor xenograft angiogenesis using zebrafish embryos. The oxidative stress and AKT-signaling-modulating abilities of withanolides were highlighted in cancer treatments, which indicated that further assessments of their angiogenesis-modulating potential are necessary in the future. Moreover, targeting AKT for inhibiting AKT and its AKT signaling shows the potential for anti-migration and anti-angiogenesis purposes for future application to withanolides. This particularly holds for investigating the anti-angiogenetic effects mediated by the oxidative stress and AKT signaling pathways in withanolide-based cancer therapy in the future.
Highlights
Cell migration is essential in development, angiogenesis, metastasis, and tumorigenesis [1]
Because the zebrafish embryos are transparent, oxidative stress change is easy to observe by direct staining in the following studies
Zebrafish are applied in several angiogenesis studies, such as anti-angiogenesis drug screening [15,16], angiogenesis disease [17], angiogenesis in regeneration [18], and tumor angiogenesis [19,20]
Summary
Cell migration is essential in development, angiogenesis, metastasis, and tumorigenesis [1]. Accumulated evidence showed that metastasis shares some signaling pathways with migration and angiogenesis. Metastasis, and angiogenesis, such as oxidative stress and the AKT serine/threonine kinase (AKT) signaling pathway. The relationships between oxidative stress, AKT signaling, and angiogenesis in withanolide treatments lack systemic investigation. This review analyzed the relationship between oxidative stress, AKT, its downstream effects, and angiogenesis from reports utilizing the outcomes of experiments with zebrafish embryos. Selected withanolides with oxidative stress and AKT-signaling-modulating effects were summarized, but their potential applications to angiogenesis regulation are rarely investigated. We propose an approach to identify the potential anti-angiogenetic withanolides using inhibitory effects on AKT and AKT signaling as biomarkers and potential drug candidates
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