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

## TL;DR

This paper reviews how natural chemicals can inhibit HIF-1α in breast cancer, potentially offering new treatment options by reducing tumor growth and metastasis.

## Contribution

The paper compiles preclinical evidence on natural HIF-1α inhibitors and highlights their potential for future breast cancer therapies.

## Key findings

- Natural phytochemicals like curcumin and polyphenols show promise as HIF-1α inhibitors in breast cancer.
- Preclinical studies demonstrate reduced angiogenesis and tumor progression with these inhibitors.
- Challenges include bioavailability and dose optimization for effective clinical application.

## 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.