The Effect of HIF-Targeting Oligonucleotides on Breast Cancer

HIF-1α, a transcription factor that stimulates the cellular response to a nutrient deficiency, typically oxygen, is overexpressed in and plays a major part in the aggressiveness of many cancers, especially breast cancer. The promoters of several oncogenes, including HIF-1α, contain guanine-rich sequences capable of forming quadruplex DNA (HIF-1α q, 22 bp).  I hypothesized that the treatment of four breast cancer cell lines (MCF-7, SKBR-3, MDA-MB-231, and MDA-MB-468) with an oligonucleotide encoding HIF-1α q would reduce HIF expression and thus induce cell death. MTT assays showed dose and time-dependent decreases in cell viability following HIF-1α q treatment, which was mostly likely the result of the decreased HIF expression demonstrated by Western blots. Confocal and flow cytometry analyses showed high uptake of the oligonucleotides into the cell and then the nucleus. Oligonucleotides encoding the HIF-1α q sequence appear to be potent anti-cancer agents with great clinical potential.