A compound found in green tea may be an effective way to kill oral cancer cells without damaging healthy cells.
Earlier studies showed the compound called epigallocatechin-3-gallate (EGCG) killed oral cancer cells, but researchers didn’t how it worked, says Joshua Lambert, associate professor of food science at Penn State University.
“EGCG is doing something to damage the mitochondria and that mitochondrial damage sets up a cycle causing more damage and it spirals out, until the cell undergoes programmed cell death.
“It looks like EGCG causes the formation of reactive oxygen species in cancer cells, which damages the mitochondria, and the mitochondria responds by making more reactive oxygen species.”
As this mitochondrial demise continues, the cancer cell also reduces the expression of antioxidant genes, further lowering its defenses.
“So, it’s turning off its mechanism of protection at the same time that EGCG is causing this oxidative stress,” Lambert says.
The compound did not cause the same reaction in normal cells—in fact it appeared to increase the protective capabilities of the cell, according to the study published online in the journal Molecular Nutrition and Food Research.
For the study, researchers looked at normal human oral cells side-by-side with human oral cancer cells to determine how EGCG was affecting cancer cells differently than normal cells.
They grew the normal and cancer cells on petri dishes and then exposed them to EGCG, the major polyphenol found in green tea, at concentrations typically found in the saliva after chewing green-tea chewing gum.
At various times, the researchers would collect the cells and check for oxidative stress and signs of antioxidant response.
“We also took a lot of pictures, so we could use fluorescent dyes that measure mitochondrial function and oxidative stress and actually see these things develop,” says Lambert, who worked with Jong-Yung Park, a research technician, and Ling Tao, a doctoral candidate in food science.
A protein called sirtuin 3—SIRT3—is critical to the process, the researchers say.
“It plays an important role in mitochondrial function and in antioxidant response in lots of tissues in the body, so the idea that EGCG might selectively affect the activity of sirtuin 3 in cancer cells—to turn it off—and in normal cells—to turn it on—is probably applicable in multiple kinds of cancers,” Lambert says.
The study builds on earlier research on how EGCG affected oral cancer, a disease that is expected to kill more than 8,000 people in the United States this year.
“We’ve published one paper previously just looking at the effect of these green tea polyphenols on oral cancer cells in cultures, and there have been other papers published using oral cancer cells and at least a couple of animal model studies that have looked at oral cancer and prevention of oral cancer,” Lambert says.
The next step will be to study the mechanism in animals. If those tests and human trials are successful, the researchers then hope to create anti-cancer treatments that are as effective as current treatments without the harmful side effects.
“The problem with a lot of chemotherapy drugs—especially early chemotherapy drugs—is that they really just target rapidly dividing cells, so cancer divides rapidly, but so do cells in your hair follicles and cells in your intestines, so you have a lot of side effects,” Lambert says.
“But you don’t see these sorts of side effects with green tea consumption.”
The American Institute for Cancer Research supported the research.
Source: Penn State