Diet restriction and cancer development

It is well established that dietary restriction, which involves limiting nutrient intake below normal levels but without reaching malnutrition, extends lifespan, youthfulness, age-associated traits and diseases, including cognitive deterioration and cancer in most, if not all, species – probably including humans, This might be due to the evolutionary advantage of keeping alive under suboptimal nutrient availability, and postponing reproduction until food is plentiful.

But dietary restriction does not affect all types of cancer similarly, raising questions about the generality of its effects and its mode of action in cancer. ‘Writing in Nature 9th April 2009 , Kalaany and Sabatini and with a commentary by Brunet describe the behaviour of address these questions in both human tumour cells and animal models of human cancer.
When human-tumour cell lines are implanted into mice, some lines cannot expand if the animals’ caloric intake is reduced by 40% for a period of 3 weeks. The cell lines that were resistant to the antitumour benefits of this nutrient restriction carried mutations that led to the constitutive (continuous) activation of the signalling pathway mediated by the hormone insulin. These cell lines had mutations that activated the enzyme PI3K, a key component of the insulin signalling pathway, or inactivated PTEN phosphatase, an enzyme that counteracts PI3K action. So it seems that, to exert its anticancer benefits, limited dietary intake must reduce insulin-mediated signalling.
In further experiments, only tumours with an active PI3K pathway were resistant to dietary restriction. What’s more, activating this pathway was both necessary and sufficient for tumour resistance to reduced food intake. Finally, the FOXO proteins, which are major down stream targets of the PI3K signalling and affect gene transcription , seems to execute the effects pof dietary restriction as FOXO transcription factors were inactivated in the tumours resistant to reduced nutrient intake.
There was an increase in programmed cell death (apoptosis). Reduced food intake could affect other cellular processes that contribute to tumour size, cell proliferation; or trigger autophagy, a ‘self-eating’ cellular process that would help to recycle nutrients and ward off cancer by eliminating damaged proteins or organelles; or it might help to reduce the growth of new blood vessels in tumours – a process known as angiogenesis – thus affecting the tumour micro environment rather than the tumour cells.
Dietary restriction in moderation might reduce the chances of developing cancer along with not smoking.
Brunet 2009 When restriction is good . Nature vol 458 pp 713-4
Kalaany and Sabatini 2009 Tumours with P12K activation are resistant to dietary restriction. Nature vol 458 pp 725 – 731

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Martin Eastwood
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