A promising brew?
Green tea antioxidant is studied for anti-cancer properties
BY JIM HOWE
Can drinking green tea prevent cancer?
Probably not, although scientists are unlocking the brew’s benefits.
“Hundreds of millions of people drink green tea every day. If it were a miracle cancer drug, we would have known it by now,” says Upstate researcher Stewart Loh, PhD.
An antioxidant in green tea, however, could point the way to new cancer-fighting drugs through its interaction with an anti-cancer protein in the body, according to a recent study.
The labs of Loh and Upstate colleague Michael Cosgrove, PhD, took part in the study, published in the journal Nature Communications. They are professors of biochemistry and molecular biology, and Loh is also that department’s vice chair.
The science in a nutshell
Antioxidants help to undo the damage caused during the normal process of oxygen metabolism, by which the body gets energy. Green tea’s major antioxidant is called EGCG, which stands for epigallocatechin-3 gallate.
In this model, the p53 tumor suppressor (the multicolored molecule), binds to DNA (the blue strand) and activates genes that defend against cancer. Green tea (the plant and dried leaves at top), contains the compound EGCG (shown by the green dots), which binds to p53 and helps it resist being degraded by cancer cells.
(Model image courtesy of Özlem Demir, Emilia P. Barros, Tavina L. Offutt, Mia Rosenfeld and Rommie E. Amaro, from “An Integrated View of p53 Dynamics, Function, and Reactivation.” Current Opinion in Structural Biology, Volume 67, April 2021, Pages 187-194. ISSN 0959-440X)
Green tea is unfermented or lightly fermented. Black tea is fully fermented, and it is the most commonly consumed tea in the United States and around the world. The tea served in most restaurants and the tea bags found in most home kitchens are black tea. EGCG is also found in black tea, but at about one-eighth the level of green tea.
EGCG is also available as an herbal supplement, but Loh and Cosgrove advise against trying to consume it that way, because its safety and effectiveness are unknown. Both the National Cancer Institute and the National Center for Complementary and Integrative Health say the evidence is inconclusive on whether anything in green tea can prevent cancer.
The anti-cancer protein is called p53. It is nicknamed the “guardian of the genome” because it can repair DNA damage to cells, keep cells from multiplying too rapidly and destroy cancer cells.
“Now we find that there is a previously unknown, direct interaction between EGCG and p53, which points to a new path for developing anti-cancer drugs. Our work helps to “explain how EGCG is able to boost p53’s anti-cancer activity, opening the door to developing drugs with EGCG-like compounds,” says the study’s lead author, Chunyu Wang, MD, PhD, a professor at Rensselaer Polytechnic Institute in Troy, New York.
Wake up ‘the good guy,’ but carefully
Loh, who has been studying p53 for 25 years, calls it “arguably the most important protein in your body when it comes to cancer.
“P53 is the good guy. That's the molecule that’s keeping you from getting cancer,” Loh says.
He explains the drama playing out at a microscopic level: “P53 is a tumor suppressor, so you’re trying to wake it up, and that entails making it active, but anything that’s too active is going to be a problem. So, we’re trying to wake it up just enough.
“MDM2 (or murine double minute 2, another protein) is the one that's sort of controlling p53. Each is needed for the other because p53 protects you against cancer by killing cancer cells, and if it’s too active, it’ll kill everything. So the MDM2 protein reins in the activity.
“But when MDM2 is overactive, which happens in a lot of cancers, then it reduces the amount of p53 in your cells by so much that the cancer takes over. EGCG competes and helps disrupt that interaction between those two proteins, so that allows p53 activity to increase.”
A previously unknown interaction
Loh notes that it is generally thought that half of all human cancers are driven by mutations in p53.
“And in the other half, p53 is not mutated. It’s normal.
“So why do you get cancer? It’s because of things like MDM2. It's the way that p53 is regulated, gets screwed up by either mutation, or something else. EGCG targets roughly half of human cancers.”
He says their research was published because it’s the first time anyone showed that EGCG binds to this important tumor suppressor.
Loh’s lab helped make the form of p53 protein needed for the study, a difficult and tricky process.
Cosgrove’s lab helped process the research data by using a technique developed in his lab and by showing that the protein’s shape changed during interactions, which is a key to understanding how it works.
Also assisting in the study were Allen Blayney and Jeung Hoi-Ha from Loh’s lab and Michael Connelly and Ashley Canning from Cosgrove’s lab. Both labs receive funding from the National Cancer Institute for their research.