While nicotine is not actually carcinogenic, it is considered to be largely responsible for the addictive nature of cigarettes, and therefore features as a key ingredient in many products that are intended to help people stop smoking, such as nicotine patches. However, a new study in the Journal of Experimental Medicine provides evidence that nicotine may be significantly more harmful than previously thought, as it helps cancers spread from the lungs to the brain.
It is thought that up to 40 percent of lung cancer sufferers develop some form of metastasis, whereby cancerous cells break away from the main tumor and travel through the bloodstream to other organs. Some 90 percent of lung cancer deaths are attributed directly to these metastases, with metastatic brain cancer being among the most common.
To conduct their research, the study authors examined 281 lung cancer patients, immediately noticing that brain cancer was considerably more common among those who smoked cigarettes. Given that nicotine is able to cross the blood-brain barrier, the researchers hypothesized that this compound is somehow involved in promoting metastatic brain cancer.
The team tested this theory using mice that had been genetically modified to develop lung cancer. When these mice were treated with nicotine, they suddenly became much more likely to develop brain tumors as well.
Further analysis revealed that nicotine binds onto receptors on the surface of microglia, which are a type of immune cell found in the brain. This then causes these microglia to switch from their so-called M1 form – which destroy tumors – to an alternate form known as M2, which actually supports the growth of tumors by inhibiting certain immune responses.
When examining the mice’s brain tumors, the researchers discovered that they contained high numbers of M2 microglial cells and relatively few M1 microglia. Faced with all of this evidence, the authors conclude that nicotine does indeed help lung cancer spread to the brain, thanks to its effect on microglial cells.
Fortunately, though, the situation is far from hopeless, as the researchers also identified a compound called parthenolide that prevents microglia from morphing into their M2 form, thereby lowering the risk of brain metastasis. When mice were treated with parthenolide, they no longer developed brain tumors, indicating that the effects of the nicotine had been counteracted.
Fortunately, parthenolide is known to be safe and occurs naturally in a herb called feverfew, making it an excellent candidate to help protect smokers from brain metastasis.
Commenting on these findings, study author Kounosuke Watabe explained in a statement that "traditional chemotherapy drugs can't cross the blood-brain barrier, but parthenolide can, and thus holds promise as a treatment or possibly even a way to prevent brain metastasis."