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Targeting hypoxia-inducible factor 1 (HIF-1) signaling with natural products toward cancer chemotherapy

Abstract

Tumor cells are often exposed to hypoxia because of the lower oxygen supply deep inside the tumor tissues. However, tumor cells survive in these severe conditions by adapting to hypoxic stress through the induction of hypoxia-inducible factor 1 (HIF-1) signaling. HIF-1 activation is responsible for the expression of numerous HIF-1 target genes, which are related to cell survival, proliferation, angiogenesis, invasion, metastasis, cancer stemness, and metabolic reprogramming. Therefore, HIF-1 is expected to be a potential pharmacological target for cancer therapy. Small molecules derived from natural products (microbial origin, plant-derived, or marine organisms) have been shown to have unique chemical structures and biological activities, including HIF-1 inhibition. Several studies identified HIF-1 inhibitors from natural products. In this review, we summarize the current HIF-1 signaling inhibitors originating from natural products with a variety of modes of action, mainly focusing on microbial metabolites.

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Acknowledgements

This work was financially supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan [17H06401 (H.K.) and 19H02840 (H.K.)] and Grants for Research on the Innovative Development and the Practical Application of New Drugs for Hepatitis B Grant [20fk0310112 (H.K.), 21fk0310112 (H.K.)] and for the Platform Project for Supporting Drug Discovery and Life Science Research [21am0101092 (H.K.)] from the Japan Agency for Medical Research and Development (AMED), Japan.

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Ikeda, H., Kakeya, H. Targeting hypoxia-inducible factor 1 (HIF-1) signaling with natural products toward cancer chemotherapy. J Antibiot 74, 687–695 (2021). https://doi.org/10.1038/s41429-021-00451-0

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