Nav: Home

Beta-cryptoxanthin, a carotenoid, inhibits nicotine-linked lung cancer development in mice

November 01, 2016

BOSTON (November 1, 2016)--Beta-cryptoxanthin (BCX), a carotenoid pigment compound found primarily in plants, reduces the number and invasiveness of tumors in mouse and cell models of lung cancer, report scientists from the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University (USDA HNRCA). The findings were published in the November issue of Cancer Prevention Research.

A team led by Xiang-Dong Wang, M.D., Ph.D., senior scientist and director of the Nutrition and Cancer Biology Laboratory at the USDA HNRCA, studied the effect of BCX using a mouse strain that develops lung tumors when exposed to NNK--a nicotine-derived carcinogen found in tobacco products and some electronic-cigarette liquids. For two weeks prior to a single high dose of NNK and for 16 weeks after, mice were given BCX in their normal daily diet, at concentrations of either one or 10 milligrams per kilogram of food. The team calculated that these doses are equivalent to approximately 0.087 and 0.87 milligrams of daily BCX intake in humans (eating a tangerine or cup of sweet red peppers per day, for example).

At the end of the experimental period, mice fed BCX developed on average 50 to 60 percent fewer tumors than mice not fed BCX, with a slightly stronger reduction in the group that ate more BCX. No differences in tumor size or type were observed. In parallel laboratory experiments, cultured human lung cancer cells that were treated with varying doses of BCX had significantly reduced migration and invasion capacity compared with non-treated cells.

The team's findings corroborate human epidemiological studies that have found an association between higher BCX intake and lower risk of lung cancer in current smokers from North America and Asian countries. In addition, prior work from Wang's laboratory demonstrated that BCX can decrease cigarette smoke-induced lung inflammation and nicotine-related emphysema in animal models.

"For smokers, tobacco product users or individuals at higher risk for tobacco smoke exposure, our results provide experimental evidence that eating foods high in BCX may have a beneficial effect on lung cancer risk, as suggested by previous epidemiological studies. We emphasize that the best way to get BCX is from food, which include other nutrients that can have additive or complementary effects," said Wang, who is also a professor at the Friedman School of Nutrition Science and Policy at Tufts. "The amounts of BCX used in our study were easily achieved by eating a modest amount of sweet red peppers, pumpkin, oranges, or other BCX-rich foods."

Wang and his colleagues found that BCX likely reduces tumor number and invasiveness by inhibiting the production of a specific nicotine receptor, alpha7 nAChR. Prior studies have suggested that exposure to nicotine and NNK triggers overproduction of these nicotine receptors in lung tissue, which can lead to increased cell growth, cell migration and risk for tumor formation. In the current study, the research team found that BCX-fed mice had roughly half the alpha7 nAChR levels in their lung tissue after NNK exposure compared to mice on a normal diet. Additional laboratory experiments revealed that BCX suppresses the expression of alpha7 nAChR and associated signaling pathways that promote cell growth and migration, and that BCX had no effect on cells lacking the alpha7 nicotine receptor.

"Our study is the first to demonstrate that BCX prevents overproduction of the alpha7 nicotine receptor, which represents a possible mechanism for how BCX inhibits the development of lung tumors," Wang said. "While we believe BCX has preventive or therapeutic potential against lung cancer, additional studies are required as human biology cannot be fully mimicked by cell and animal models. We are now further investigating the molecular interactions between BCX and lung cancer, and exploring the possibility for small-scale human clinical trials."

Along with alpha- and beta-carotene, BCX is a provitamin A carotenoid that the human body metabolizes into vitamin A. Previous clinical trials, as well as animal studies conducted by Wang's laboratory, have found that supplementation with extremely high levels of retinyl ester--a form of vitamin A found in animal products--and beta-carotene is associated with increased risk of lung cancer, and that supplementation with beta-carotene has no preventative effect. In the current study, Wang and his colleagues found that the unique preventative effects of BCX against lung cancer risk are likely due to BCX itself and are unrelated to biologically generated vitamin A. The team are further investigating the underlying mechanisms.

As a carotenoid, BCX is part of the family of pigment compounds responsible for red, orange and yellow colors in fruits and vegetables. According to the USDA Agricultural Research Service's Food Composition Databases, foods containing the highest amounts of BCX include sweet red peppers, paprika, butternut squash, persimmons, tangerines, papaya, peaches and oranges. The Recommended Dietary Allowances of vitamin A for individuals aged 14 or older are 900 micrograms per day for males, 700 micrograms per day for adult females, and 750 and 1,200 micrograms per day for pregnant and lactating females respectively, according to the Food and Nutrition Board at the Institute of Medicine of the National Academies. Excessive vitamin A intake can result in liver damage and birth defects.
Additional authors include lead study author Anita R. Iskandar, Ph.D., graduate of the Friedman School of Nutrition Science and Policy at Tufts and former postdoctoral associate, Benchun Miao, Ph.D., former postdoctoral fellow, Xinli Li, Ph.D., visiting scientist, Kang-Quan Hu, M.S., research associate, and Chun Liu, M.D., M.S./M.P.H., scientist II, all of the Nutrition and Cancer Biology Laboratory at the USDA HNRCA.

The authors were supported by awards from the National Cancer Institute of the National Institutes of Health (CA176256) and the United States Department of Agriculture's Agricultural Research Service.

Iskandar, A.R., Miao, B., Li, X., Hu, K., Liu, C., and Wang, XD. "β-Cryptoxanthin reduced lung tumor multiplicity and inhibited lung cancer cell motility by down-regulating nicotinic acetylcholine receptor α7 signaling," Cancer Prev Res; 9(11); 1-12. DOI: 10.1158/1940-6207.CAPR-16-0161.

About the Jean Mayer USDA Human Nutrition Research Center on Aging and the Friedman School of Nutrition Science and Policy

For three decades, the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University has studied the relationship between good nutrition and good health in aging populations. Tufts research scientists work with federal agencies to establish the USDA Dietary Guidelines for Americans, the Dietary Reference Intakes, and other significant public policies. The Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy at Tufts University is the only independent school of nutrition in the United States. The school's eight degree programs - which focus on questions relating to nutrition and chronic diseases, molecular nutrition, agriculture and sustainability, food security, humanitarian assistance, public health nutrition, and food policy and economics - are renowned for the application of scientific research to national and international policy.

Tufts University, Health Sciences Campus

Related Lung Cancer Articles:

'Social smokers' face disproportionate risk of death from lung disease and lung cancer
'Social smokers' are more than twice as likely to die of lung disease and more than eight times as likely to die of lung cancer than non-smokers, according to research presented at the European Respiratory Society International Congress.
Lung cancer therapy may improve outcomes of metastatic brain cancer
A medication commonly used to treat non-small cell lung cancer that has spread, or metastasized, may have benefits for patients with metastatic brain cancers, suggests a new review and analysis led by researchers at St.
Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Lung transplant patients face elevated lung cancer risk
In an American Journal of Transplantation study, lung cancer risk was increased after lung transplantation, especially in the native (non-transplanted) lung of single lung transplant recipients.
Proposed cancer treatment may boost lung cancer stem cells, study warns
Epigenetic therapies -- targeting enzymes that alter what genes are turned on or off in a cell -- are of growing interest in the cancer field as a way of making a cancer less aggressive or less malignant.
Are you at risk for lung cancer?
This question isn't only for people who've smoked a lot.
Better equipped in the fight against lung cancer
Lung cancer is the third most common type of cancer in Germany and the disease affects both men and women.
New liquid biopsy-based cancer model reveals data on deadly lung cancer
Small cell lung cancer (SCLC) accounts for 14 percent of all lung cancers and is often rapidly resistant to chemotherapy resulting in poor clinical outcomes.
Cancer drug leads to 'drastic decrease' in HIV infection in lung cancer patient
Doctors in France have found the first evidence that a cancer drug may be able to eradicate HIV-infected cells in humans.
More Lung Cancer News and Lung Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at     You can read The Transition Integrity Project's report here.