How Caffeine Fights Cancer

Caffeinated drinks may help prevent skin cancer by inhibiting a DNA repair pathway, thus killing potentially precancerous cells.

By | August 15, 2011

WIKIMEDIA COMMONS, JULIUS SCHORZMAN

Epidemiological studies have shown that drinking caffeinated beverages reduces one’s chances of developing some types of cancer, including UV-associated skin cancer. Now, researchers propose a possible mechanism for this observation—the inhibition of a DNA repair pathway that sensitizes cells to death after sun exposure.

The results, published today (August 15) in the Proceedings of the National Academy of Sciences, lend support to the idea that caffeine could be added to sunblock to increase its protective effects.

“At the cellular level, they’re showing that caffeine…is working in this way of inducing an apoptotic mechanism,” said cancer epidemiologist Joanne Kotsopoulos of the University of Toronto, who was not involved in the research. “It’s biologically plausible, and it has good implications” for potential skin cancer prevention strategies.

Several epidemiologic studies have suggested that coffee and tea drinkers are at a decreased risk for a variety of human cancers, including UV-associated skin cancer. A 2007 study of nearly 94,000 women, for example, found that woman who drank caffeinated coffee on a daily basis had a 10 percent lower risk of nonmelanoma skin cancer. Six or more cups of coffee a day translated to a 30 percent reduction in risk. Mouse studies have also confirmed the link, with both ingested and topically-applied caffeine lowering skin cancer rates in the animals. But exactly how the stimulant protected against cancer remained mysterious.

One possibility is the drug’s inhibition of ataxia telangiectasia and Rad3-related (ATR), a large protein kinase that senses incomplete DNA replication—often a result of DNA damage—and signals the cell to not divide. By inhibiting ATR activity, caffeine could make cells more likely to die in response to UV damage, preventing damaged cells from ever becoming cancerous.

Normal mitosis occurs when replication is complete prior to chromatin condensation (left). When the ATR mechanism fails to alert the cell to incomplete DNA replication, chromatin condensation begins before replication is complete (right). See an animation of this process here.
Normal mitosis occurs when replication is complete prior to chromatin condensation (left). When the ATR mechanism fails to alert the cell to incomplete DNA replication, chromatin condensation begins before replication is complete (right). See an animation of this process here.
COURTESY OF PAUL NGHIEM

To test this hypothesis, cancer biologist and dermatologist Paul Nghiem of the University of Washington Dermatology examined mice that were sensitive to UV damage, and thus prone to skin cancer. Because knocking out ATR activity entirely would've killed the mice, Nghiem and his colleagues developed a transgenic mouse model with an additional, mutated copy of the protein. The mutated version competed with the wildtype protein and effectively reduced ATR activity without eliminating it altogether.

Exposing the mice to UV radiation, the researchers found that it took transgenic mice about 3 weeks longer to develop skin cancer than their transgene-negative littermates. After 19 weeks of UV treatment, the transgenic mice had 69 percent fewer tumors than the controls. Furthermore, the tumors that the transgenic mice did develop were less likely to advance to the more serious form of the disease, squamous cell carcinoma (SCC).

The researchers also tested the skin cells from the mice in vitro, adding caffeine shortly after UV exposure. While caffeine caused the cells from the control mice to become sensitized to the radiation, increasing the rate of apoptosis, it had no effect on the cells that already had reduced ATR activity. “So it argues that caffeine is working on the same pathway as ATR,” Nghiem said.

The caffeine molecule itself is also known to act as a sunscreen, blocking the penetration of UV rays, Nghiem said. “Therefore adding it to sunscreens may make sense for two reasons—it’s directly a sunscreen, and completely independently, it has this effect on ATR.”

There are still some remaining questions and studies to be done, such as actually applying caffeine to the mice’s skin and seeing if it confers additional cancer protection. “I think there’s good potential to keep investigating this,” Kotsopoulos said. “I mean, how easy would that be? To formulate [caffeine] into existing sunscreens as an additive?”

Alternatively, a drug other than caffeine that targets ATR may be used, said biophysicist Douglas Brash of Yale University’s School of Medicine. “Caffeine was an interesting historical way of discovering this mechanism,” he said, “but now that we know the mechanism…maybe we hunt for some other drug that’s more specific.” Indeed, drugs that target the ATR pathway are currently in clinical trials for solid cancers, in combination with DNA damaging drugs. Given the results of the new study, such drugs may be able to be repurposed to fight skin cancer as well, Brash said.

M. Kawasumia et al., “Protection from UV-induced skin carcinogenesis by genetic inhibition of the ataxia telangiectasia and Rad3-related (ATR) kinase,” Proceedings of the National Academy of Sciences, doi/10.1073/pnas.1111378108, 2011.

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Comments

Avatar of: D L Laux

Anonymous

August 17, 2011

Don't tell Starbucks.  They'll raise the price of their coffee even more.

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Posts: 0

August 17, 2011

Don't tell Starbucks.  They'll raise the price of their coffee even more.

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Posts: 0

August 17, 2011

Don't tell Starbucks.  They'll raise the price of their coffee even more.

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Posts: 0

September 16, 2011

The DNA-repair inhibiting effect of Caffeine is well known, and it enhances the cytocidal effects of anticancer drugs and radiation. But it is nice to know how it works.

/Mikael Ros

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Posts: 0

September 16, 2011

The DNA-repair inhibiting effect of Caffeine is well known, and it enhances the cytocidal effects of anticancer drugs and radiation. But it is nice to know how it works.

/Mikael Ros

Avatar of: Mikael Ros

Anonymous

September 16, 2011

The DNA-repair inhibiting effect of Caffeine is well known, and it enhances the cytocidal effects of anticancer drugs and radiation. But it is nice to know how it works.

/Mikael Ros

Avatar of: Miracana

Anonymous

September 20, 2011

now I know why I like coffe

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Posts: 0

September 20, 2011

now I know why I like coffe

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Posts: 0

September 20, 2011

now I know why I like coffe

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Posts: 0

September 30, 2011

Nice, now I can reduce potential skin cancer which runs in my family by drinking caffeinated beverages and then drop from a cardiac arrhythmia.

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Posts: 0

September 30, 2011

Nice, now I can reduce potential skin cancer which runs in my family by drinking caffeinated beverages and then drop from a cardiac arrhythmia.

Avatar of: JHolland

Anonymous

September 30, 2011

Nice, now I can reduce potential skin cancer which runs in my family by drinking caffeinated beverages and then drop from a cardiac arrhythmia.

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