Work

Natural Phytochemicals as Inhibitors of HIF-1α in Breast Cancer: Review of Preclinical Evidence and Future Prospects

Year: 2026

Type: article

Abstract: Breast cancer is the most prevalent form of cancer among women globally. The hypoxic microenvironment resulting from the rapid oxygen consumption of rapidly dividing cancer cells causes the accumulation of hypoxia-inducible factor-1α (HIF-1α) due to reduced catalytic activity of prolyl hydroxylase domain 2 (PHD2) and Von Hippel-Lindau (VHL). Under physiological conditions, HIF-1α regulates cell response to hypoxic environments. Activating genes are involved in glycolysis, angiogenesis, and erythropoiesis. However, the sustained hypoxic environment in breast cancer facilitates metastasis, immune evasion, and drug resistance. Consequently, HIF-1α is a key target in breast cancer treatment, and such inhibitors of HIF-1α may prove to be a viable treatment option. Increasing evidence suggests that natural chemicals, such as polyphenols, isothiocyanates, curcumin, and alkaloids, are inhibitors of HIF-1α. Preclinical studies using animal models and breast cancer cell lines indicate significant reductions in angiogenesis, despite challenges of heterogeneity, bioavailability, and dose optimization. This review intends to summarize current evidence on natural inhibitors of HIF-1α and potential future studies.

Source: Current Issues in Molecular Biology

DOI: 10.3390/cimb48010121

Authors: Ivan Dam, Eric Liu, Abida Ali, Chikezie O. Madu, Yi Lu

Institutions: University of Memphis, University of Tennessee Health Science Center

Language: English

Topic: Cancer, Hypoxia, and Metabolism

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,654