Vitamin supplements may be linked to increased cancer risk, suggests new research

Lung cancer progression relies on angiogenesis, which is a response to hypoxia typically coordinated by hypoxia-inducible transcription factors (HIFs); but growing evidence indicate that transcriptional programs beyond HIFs control tumor angiogenesis. A recent study published in J Clin Invest, the researchers showed that the redox-sensitive transcription factor BTB and CNC homology 1 (BACH1) controls the transcription of a broad range of angiogenesis genes.

BACH1 is stabilized by lowering reactive oxygen species levels; consequently, angiogenesis gene expression in lung cancer cells, tumor organoids, and xenograft tumors increased substantially following vitamin C and E and N-acetylcysteine administration in a BACH1-dependent fashion under normoxia. Moreover, angiogenesis gene expression increased in endogenous BACH1–overexpressing cells and decreased in BACH1-knockouts in the absence of antioxidants.

BACH1 levels also increased upon hypoxia and following administration of prolyl hydroxylase inhibitors in both HIF1a-knockout and wild-type cells. BACH1 was found to be a transcriptional target of HIF1α but BACH1’s ability to stimulate angiogenesis gene expression was HIF1a independent.

Antioxidants increased tumor vascularity in vivo in a BACH1-dependent fashion, and overexpressing BACH1 rendered tumors sensitive to anti-angiogenesis therapy. BACH1 expression in tumor sections from lung cancer patients correlates with angiogenesis gene and protein expression.It was thus concluded that BACH1 is an oxygen- and redox-sensitive angiogenesis transcription factor.

Reference: Ting Wang et al,J Clin Invest, DOI: 10.1172/JCI169671