Killer Chili Peppers

Catalyst Volume 8

Have you experienced that burning sensation on your tongue after eating a spicy pepper? This reaction is caused by capsaicin, a colorless and odorless compound present in chili peppers. Spiciness is measured using Scoville heat units (SHU), which are based on the concentration of capsaicin in the pepper. Jalapeños have a range of 3,500 — 10,000 Scoville units, habaneros have a range of 100,000 — 350,000 Scoville units, and the world’s hottest pepper, the Trinidad Moruga Scorpion, has a range of 2,000,000 — 2,200,000 Scoville units. However, they all pale in comparison to pure capsaicin, which scores around 16 million Scoville heat units.

Capsaicin, however, does more than just add heat to your favorite foods; it has also been found to negatively affect important immune cells. In 2014, researchers at the Asan Medical Center in Seoul, South Korea found that capsaicin inhibits natural killer (NK) cells, a type of cell that is important for the surveillance of cancer.¹ NK cells use cytokine signaling molecules such as interferon-γ and tumor necrosis factor-α to target and lyse cancer cells.² Capsaicin directly decreases the cytotoxicity of NK cells by reducing cytokine production. In fact, extended exposure to capsaicin can kill NK cells.¹ NK cell malfunctions have been shown to lead to higher rates of tumor formation and cancer metastasis,³ and many patients suffering from cancer exhibit defects in the function of NK cells.⁴ Since capsaicin has negative effects on NK cells, capsaicin may also have deleterious effects on other immune cells that protect us from cancer and other ailments.

Several studies have suggested some correlation between tumor formation and capsaicin consumption. In one study, five groups of mice were fed different levels of capsaicin for 35 days, with one group being fed no capsaicin as a control. 10% of the mice that were fed varying levels of capsaicin developed adenocarcinomas of the duodenum (gastrointestinal tumors) while no control mice developed tumors.⁵ Another paper by López-Carrillo et al. studied the correlation between capsaicin intake through chili peppers consumption and gastric cancer incidences in Mexico.⁶ They found that people who consumed high levels of capsaicin, about 90 — 250 mg daily, were at a statistically higher risk for gastric cancer than those who had a lower consumption rate. 90 — 250 mg of capsaicin, however, corresponds to about 9 — 25 jalapeño peppers every single day, so most people are not at a higher risk.

Despite its apparent carcinogenicity, capsaicin may also have therapeutic capabilities in cancer treatment. Studies have shown that capsaicin is so potent that it can actually inhibit the growth of leukemia, hepatoma, glioblastoma, and colon cancer cells.⁷ In one study, gastric cancer cells treated with capsaicin at concentrations of 10, 50, and 200 μM actually underwent apoptosis, or programmed cell self-destruction, at a higher rate than normal epithelial cells under the same conditions. Capsaicin is able to induce apoptosis in cells by activating p53, a tumor suppressor gene commonly dubbed as “guardian of the genome.” This gene also functions to activate DNA repair genes, pause the cell replication cycle, and initiate apoptosis when certain triggers are activated. Capsaicin was found to activate one of these triggers, causing the p53 gene to begin apoptosis. These results suggest new possible methods of cancer treatment or prevention.⁸

Perhaps in the near future, capsaicin can be manipulated for beneficial medical applications. Capsaicin presents an interesting duality—it has promising effects for cancer treatment, yet it can lead to cancer itself. In designing treatments, researchers will have to maximize the benefits of capsaicin’s cancer-fighting abilities while mitigating the potential damage to the body’s healthy cells; this tradeoff is analogous to the one made in chemotherapy today. The correlation between capsaicin and cancer may still be quite concerning. However, with moderation, all of us can continue to enjoy the burn of Sriracha and hot wings without worrying about putting our lives in danger—at least for those who can handle the heat.

References

1. Kim, H. S. et al. Carcinogenesis 2014, 35, 1652–1660.
2. Long, E. O. et al. Annu. Rev. Immunol. 2013, 31, 227–258.
3. Hann, N. et al. J. Immunol. 1981, 127, 1754–1758.
4. Saito, H. et al. Gastric Cancer 2012, 15, 27–33.
5. Toth, B.; Rogan E.; Walker, B. Anticancer Res. 1984, 4, 177–179.
6. López-Carrillo, L. et al. Int. J. Cancer. 2003, 106, 277–282.
7. Bode, A. M. et al. Cancer Res. 2011, 71, 2809–2814.
8. Chow, J. et al. BBA 2007, 1773, 565-576.

A Cup of Tea Against Cancer

Catalyst Volume 8

Green tea, made from the leaves of Camellia sinensis, has come a long way from its humble origins in China to its current status as the second most popular beverage worldwide. According to Chinese mythology, Shennong, the legendary ruler of China in approximately 2370 BC, drank the first cup of green tea that was brewed when a tea leaf fell into his boiled water.¹ Despite his title as the divine healer, Shennong could not have possibly realized the numerous health benefits contained in the little cup. Green tea benefits health in various ways including cognitive enhancement, improvement of mental ability and alertness,² and increased reward learning through modulation of dopamine transmission.³ Tea also helps with dieting through increased fat oxidation and prevents cardiovascular disease and diabetes.⁴ Recently, several studies have also credited green tea for its ability to prevent cancer development.^1,4-6

When harvested from the tree, leaves of Camellia sinensis contain a high concentration of flavonoids. Flavonoids are members of the polyphenol group and have demonstrated anti-inflammatory, anti-allergic, and anti-mutagenic effects. In green tea, a group called catechin constitutes a large percentage of the flavonoids. This specific type of flavonoid, especially epigallocatechin gallate (EGCG), prevents the formation and growth of tumors.⁴ Normal cells take both complex and varying pathways to develop into malignant cells, but there are three crucial stages in the path to malignancy. In the initiation stage, undesirable mutations in the chromosome form due to exposure to carcinogenic substances or radiation. In the second stage of promotion, the mutation is translated and transcribed to the cytoplasm and cell membrane. The last stage is progression, during which cancer cells proliferate. By this point, accumulated mutations in chromosomes produce many genetic alterations that promote uncontrollable growth. While the numerous stages of cancer progression may complicate the search of one specific cure, they provide equal number of opportunities for regulation of carcinogenesis.⁵

The polyphenol substituents found in tea can suppress cancer at various stages in its progression. First, tea can prevent initiation by inactivating or eliminating the mutagens that can potentially damage the cell DNA. Potential mutagens are surprisingly common in our environment.⁵ Every day, we are exposed to processes that introduce dangerous reactive oxygen species (ROS) such as hydrogen peroxide and oxygen radicals that can react with DNA and induce detrimental mutations.¹ Common ionizing radiation (UV and X-rays) as well as tobacco are well-documented mutagens as well. The flavonoids contained in tea are natural scavengers that destroy these free oxygen radicals.¹ Catechin, a type of flavonoid, is especially effective at reducing free radicals by binding to ROS as well as to ferric ions, which are required to create ROS.⁶ Polyphenols of green tea can also competitively inhibit intermediates of heterocyclic aromatic amines, a new class of carcinogens, thus reducing the danger of accumulating DNA-damaging material.1 Finally, the chemical structure of the polyphenols in tea has strong affinity toward carcinogens, enabling them to bind to and neutralize the harmful substances.⁶ By blocking common cancer-initiating factors, tea lowers the chance of genetic mutations that may result in a tumor.

Substances in green tea can also prevent cancer by blocking angiogenesis, essentially starving the tumor cells.¹ Angiogenesis is the formation of network of blood vessels through cancerous growths. In smaller tumors, cancer cells can use simple diffusion to transport necessary oxygen and nutrients. However, as the number of accumulated cells increase, tumor cells send signals to surrounding host tissues to produce the proteins necessary for blood vessel generation. These blood vessels supply large amounts of oxygen and nutrients that are unavailable through passive diffusion. Catechins in green tea stop angiogenesis by interfering with the tumor cell signals. EGCG has been shown to inhibit epidermal growth factor receptor, and thus production of vascular endothelial growth factor (VEGF), which is in charge of initiating angiogenic blood vessel formation.¹ Further studies have shown direct inhibition of VEGF transcription and VEGF promoter activity in breast cancer cells by green tea extract (GTE) and EGCG.^4-6 GTE also suppresses production of protein kinase C, which regulates VEGF as well. By inhibiting the signal pathway to blood vessel formation, green tea is able to reduce the progression of angiogenesis.

Another role of tea includes preventing metastasis, which is the most common cause of cancer-related mortality.¹ Metastasis represents the full development of a tumor, in which the boundary that enclosed the cancer is broken and the tumor freely migrates to other parts of the body. Green tea’s flavonoids prevent degradation of membranes and proteins on the cell surface that promotes anchorage.¹ Once base membranes and proteins that anchor cells to specific locations disappear, tumor cells are unfettered. EGCG in green tea has been shown to block metastasis by inhibition of membrane type 1 matrix metalloproteinase (MMP), which in turn restrains MMP-2, an enzyme crucial to degradation of the extracellular matrix. In experiments, a mixture of EGCG and ascorbic acid showed a significant suppression of metastasis by 65.9%.¹

Finally, tea can prevent the unregulated proliferation of cancer cells that drives tumor formation and metastasis. Apoptosis, or the self-destruction of a cell, is actually a common and natural biological process. When a cell loses the ability to undergo apoptosis, it becomes potentially cancerous. Increasing apoptosis in cancer cells should restore balance and eliminate unrequired and harmful cells in the body. The problem lies in specifically inducing apoptosis of cancer cells without harming the normal cells, but research has shown tea’s potential in the selective promotion of apoptosis. In an experiment involving human papillomavirus 16-associated cervical cancer cells, EGCG inhibited cell growth by promoting apoptosis and cell cycle arrest.¹ In head and neck carcinoma cells, EGCG also increased the percentage of cells at phase G1, the initial growth cycle of the cell, and induced apoptosis.¹ Similar results were found by adding the extracted water-soluble fraction from green tea to mouse epidermal cells JB6, which both inhibited carcinogenesis and induced apoptosis.⁵

The extensive evidence presented here illustrates the cancer-preventive and inhibitory effects of green tea. However, we must consider that most of the data were collected through in vitro and in vivo experiments. Clinical trials with human beings have yet to confirm the preventive effects of tea polyphenol against cancer.⁵ Current research does not present significant evidence to determine the true effects of tea. On the other hand, a negative correlation has been observed between green tea consumption and cancer mortality along with general mortality rate in Japanese populations.⁵ In general, increasing the amount of green tea consumed per day indicated a reduced chance of cancer. These results suggest that tea, even with its vast number of health benefits, is not a cureall. In conjunction with regular exercise and vegetables with each meal, however, many diseases can be prevented. By drinking tea, one can partake in a tradition passed down for centuries while keeping the body healthy.

References

1. Jain, N. K. et al. Protective Effects of Tea on Human Health; CAB International: Cambridge, 2006.
2. Borgwardt, S. et al. Eur. J. Clin. Nutr. 2012, 66, 1187-1192.
3. Zhang, Q. et al. Nutr. J. 2013, 12, 84.
4. Dulloo, A. G. et al. Am. J. Clin. Nutr. 1999, 70, 1040-1045.
5. Kuroda, Y. et al. Health Effects of Tea and Its Catechins; Kluwer Academic/Plenum Publishers: New York, 2004.
6. Yammamoto, T. et al. Chemistry and Applications of Green Tea; CRC Press LLC: New York, 1997.

Don't Panic: The Science of Ebola Transmission

Catalyst Volume 8

In 2014, the Ebola virus gained notoriety for the lives it took in such a short amount of time. While the panic surrounding the virus has since died down, Ebola continues to wreak havoc in West Africa. To properly contextualize the implications of this epidemic, it is important to understand the basics of how Ebola works—how the virus itself functions, how it spreads, and how it affects the human body.

The Ebola virus is classified in the order Mononegavirales, which includes the mumps, measles, and rabies viruses.¹ There are currently five species of Ebola viruses: Zaire, Bundlibugyo, Sudan, Reston, and Tai Forest. The most lethal of these species, Zaire, is responsible for the 2014 outbreak. Ebola carries a negative-sense RNA genome that works by encoding mRNA (a type of RNA called messenger RNA) in the host cell.² The mRNA strand is translated into seven viral proteins that allow replication of the Ebola virus. Newly formed Ebola virus buds out of the cell, and once the cell dies, it lyses, or bursts, releasing viral RNA to other cells within the body.

Ebola, like the swine flu, was likely first introduced into the human population through close contact with the bodily fluid of infected animals such as chimpanzees, gorillas, monkeys, porcupines, or fruit bats, which are the virus’ natural hosts.¹ Although the virus is highly transmittable through bodily fluid, it is not an airborne disease; instead, the virus is transmitted only through direct contact of broken skin or mucous membranes with the bodily fluids of infected organisms and through direct contact with materials contaminated with these fluids.¹ People are not infectious until they develop symptoms; however, they remain infectious as long as their bodily fluids contain the virus. For example, the Ebola virus can persist in semen for up to three months subsequent to recovery. The incubation period, or time interval from infection to onset of symptoms, is 2 to 21 days.¹ The delayed onset of symptoms means that the infected individual may be unaware that he or she is carrying the disease.

During the 2014 outbreak, poor infrastructure, unsafe practices in burial ceremonies, and close contact between health-care workers and patients facilitated the spread of the virus.¹ In West Africa, improperly disposed bodily fluids contaminated materials such as clothing led to infection of healthy individuals. Burial ceremonies themselves have contributed to the transmission of Ebola in West Africa; mourners who came into direct contact with the bodies of deceased individuals contracted the disease.¹ In the U.S., the transmission of Ebola from patient Thomas Eric Duncan to nurses Nina Pham and Amber Vinson was likely caused by a breach in safety protocol; while healthcare workers are typically obligated to wear full body suits, any error in wearing or removing the suit could have exposed the nurses to Duncan’s bodily fluids.⁴

Ebola’s initial symptoms include the sudden onset of fever, fatigue, muscle pain, headache, and sore throat. These initial symptoms can often be confused with those of the flu, but they are followed by more severe ones including vomiting, diarrhea, rashes, and internal and external bleeding. While this disease has a high mortality rate of 50%,¹ its transmission is more indirect than that of more common viruses such as the flu. Because of the routes of Ebola transmission are so limited, especially in areas with developed infrastructure, the CDC and other health experts predict that an Ebola outbreak in the U.S. would be highly improbable.⁵ The events of 2014 serve as a reminder of the importance of adequate infrastructure and safety protocols in order to limit the spread of future viral epidemics.

References

1. World Health Organization. http://www.who.int/mediacentre/factsheets/fs103/en/ (accessed Nov. 1, 2014).
2. Feldmann, H. K. Arch. Virol. Suppl. 1993, 7, 81–100.
3. Mucous membrane. http://www.britannica.com/EBchecked/topic/395887/mucous-membrane (accessed Nov. 1, 2014).
4. Alexander, H. Second Texas nurse contracts Ebola after treating Thomas Eric Duncan. http://www.telegraph.co.uk/news/worldnews/ebola/11164105/Second-Texas-nurse-contracts-Ebola-after-treating-Thomas-Eric-Duncan.html (accessed Jan. 17, 2015).
5. Ebola transmission. http://www.cdc.gov/vhf/ebola/transmission/index.html?s_cid=cs_3923 (accessed Jan. 17, 2015).