Anti-Cancer Activity of Phytochemicals Targeting Hypoxia-Inducible Factor-1 Alpha

Abstract

Hypoxia-inducible factor-1 alpha (HIF-1α) is overexpressed in cancer, leading to a poor prognosis in patients. Diverse cellular factors are able to regulate HIF-1α expression in hypoxia and even in non-hypoxic conditions, affecting its progression and malignant characteristics by regulating the expression of the HIF-1α target genes that are involved in cell survival, angiogenesis, metabolism, therapeutic resistance, et cetera. Numerous studies have exhibited the anti-cancer effect of HIF-1α inhibition itself and the augmentation of anti-cancer treatment efficacy by interfering with HIF-1α-mediated signaling. The anti-cancer effect of plant-derived phytochemicals has been evaluated, and they have been found to possess significant therapeutic potentials against numerous cancer types. A better understanding of phytochemicals is indispensable for establishing advanced strategies for cancer therapy. This article reviews the anti-cancer effect of phytochemicals in connection with HIF-1α regulation.

Keywords: HIF; cancer; hypoxia; naturally derived compounds; normoxia; phytochemical.

Figure 1

Proposed signaling pathways of HIF-1α regulation by alkaloids and organosulfurs. Positive regulation is indicated by arrow lines (blue). A negative effect is shown by perpendicular lines (red).

Figure 2

Polyphenol-mediated cellular signaling pathways that are anticipated to regulate HIF-1α. Positive regulation is pointed out by arrow lines (blue). A restrictive action is indicated by perpendicular lines (red).

Figure 3

Proposed mechanisms by which terpenes regulate HIF-1α. Positive modulation is denoted by arrow lines (blue). Perpendicular lines designate an inhibitory effect (red).