Vitamin or mineral supplements could feed tumours and allow them to grow, suggests recent research, with common antioxidants like vitamins A, C, selenium and zinc – when taken additionally – possibly speeding up the growth of blood vessels in cancer.
The discovery has come as a surprise as antioxidants were believed to be protective, reports The Telegraph.
The researchers said natural levels in food were fine but if people took supplements containing antioxidants as well, the extra amount could fuel tumour growth.
The study, published in the Journal of Clinical Investigation, was carried out by the Karolinska Institutet in Sweden.
It concluded that vitamin C and other antioxidants stimulate the formation of new blood vessels in lung cancer tumours, but could also apply to all cancers and the spread of cancer.
Study leader Martin Bergö, professor at the Department of Biosciences and Nutrition, said: “Antioxidants activate a mechanism that causes cancer tumours to form new blood vessels, which is surprising, since it was previously thought antioxidants have a protective effect.
“The new blood vessels nourish the tumours and can help them grow and spread.”
Antioxidants neutralise free oxygen radicals, which can damage the body, and are commonly found in dietary supplements. But overly high doses can be harmful.
Bergö said there was “no need to fear antioxidants in normal food but most people don’t need additional amounts of them”.
“In fact, it can be harmful for cancer patients and people with an elevated cancer risk,” he said.
The team discovered that antioxidants reduce the levels of free oxygen radicals but when extra amounts are introduced, the drop in free radicals activates a protein called BACH1.
This induces the formation of new blood vessels, known as angiogenesis.
Ting Wang, doctoral student in Professor Bergö’s group said: “Many clinical trials have evaluated the efficacy of angiogenesis inhibitors, but the results have not been as successful as anticipated.
“Our study opens the door to more effective ways of preventing angiogenesis in tumours; for example, patients whose tumours exhibit high levels of BACH1 might benefit more from anti-angiogensis therapy than patients with low BACH1 levels.”
Using lung, breast and kidney tumours they found that when BACH1 was activated, either via ingested antioxidants or by over-expression of the BACH1 gene, more new blood vessels were produced but they were highly sensitive to angiogenesis inhibitors.
Wang added: “The next step is to examine how levels of oxygen and free radicals can regulate the BACH1 protein, and we will continue to determine the clinical relevance of our results.
“We’ll also be doing similar studies in other cancer forms, like breast, kidney and skin cancer.”
Study detail
Antioxidants stimulate BACH1-dependent tumour angiogenesis
Ting Wang, Yongqiang Dong, Martin Bergo et al.
Published in the Journal of Clinical Investigation on 31 August 2023
Abstract
Lung cancer progression relies on angiogenesis, a response to hypoxia typically coordinated by hypoxia-inducible transcription factors (HIFs); but growing evidence indicates transcriptional programmes beyond HIFs control tumour angiogenesis. We show that the redox-sensitive transcription factor BTB and CNC homology 1 (BACH1) controls the transcription of a broad range of angiogenesis genes. BACH1 is stabilised by lowering reactive oxygen species levels; consequently, angiogenesis gene expression in lung cancer cells, tumour organoids, and xenograft tumours increased substantially after 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 after 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 tumour vascularity in vivo in a BACH1-dependent fashion, and overexpressing BACH1 rendered tumours sensitive to anti-angiogenesis therapy. BACH1 expression in tumour sections from lung cancer patients correlates with angiogenesis gene and protein expression. We conclude that BACH1 is an oxygen- and redox-sensitive angiogenesis transcription factor.
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