期刊
PHARMACEUTICALS
卷 15, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/ph15070808
关键词
phytochemicals; tumor glycolysis; tumor hypoxia; Warburg effect; HIF-1 signaling pathway; metabolomics
资金
- grant-Partnership for the transfer of knowledge in biogenomic applications in oncology and related fields-BIOGENONCO, Project - FEDR through Competitiveness Operational Programme [10/01.09.2016, P_40_318, MySMIS 105774]
- [CNFIS-FDI-2022-0714]
The complex nature of cancer poses many challenges, but plant-derived compounds show promise in anticancer therapy. This review provides an overview of how these compounds can affect tumor glycolysis and HIF-1 pathways, emphasizing the importance of cell culture-based metabolomics in understanding the response of cancer cells to phytochemicals.
The full understanding of the complex nature of cancer still faces many challenges, as cancers arise not as a result of a single target disruption but rather involving successive genetic and epigenetic alterations leading to multiple altered metabolic pathways. In this light, the need for a multitargeted, safe and effective therapy becomes essential. Substantial experimental evidence upholds the potential of plant-derived compounds to interfere in several important pathways, such as tumor glycolysis and the upstream regulating mechanisms of hypoxia. Herein, we present a comprehensive overview of the natural compounds which demonstrated, in vitro studies, an effective anticancer activity by affecting key regulators of the glycolytic pathway such as glucose transporters, hexokinases, phosphofructokinase, pyruvate kinase or lactate dehydrogenase. Moreover, we assessed how phytochemicals could interfere in HIF-1 synthesis, stabilization, accumulation, and transactivation, emphasizing PI3K/Akt/mTOR and MAPK/ERK pathways as important signaling cascades in HIF-1 activation. Special consideration was given to cell culture-based metabolomics as one of the most sensitive, accurate, and comprising approaches for understanding the response of cancer cell metabolome to phytochemicals.
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