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Apigenin, a bioflavonoid found in celery, artichoke and the Mexican variety of oregano, induces cell death in pancreatic cancer, researchers in the United States found. The extract of cucumber balm, known as bitter melon, can play a similar role. Pancreatic cancer is one of the most dangerous cancers with a very low survival rate.
A team of scientists from the University of Illinois led by prof. Elviry de Mejia conducted research into the most aggressive types of pancreatic cancer. The risk of this type of cancer is growing – according to research by scientists from the University of London, it is one of the leading cancers in Europe and the USA – the number of cases has increased threefold in the last decade.
One of the most dangerous cancers
Currently, from the third position among gastrointestinal cancers, it begins to move to the second and accounts for about 3,8%. all malignant tumors. Usually it occurs after the age of 60, although it happens also among younger people. Usually, this cancer occurs in men. Almost 80 percent of people with pancreatic cancer have diabetes. It is extremely dangerous – about 70-90 percent. at the time of diagnosis, patients already have lymph node metastases, and the average 5-year survival is only 2%. The famous victim of this cancer was actor and dancer Patrick Swayze.
Among the factors mentioned as contributing to the development of this cancer are smoking, a high proportion of meat in the diet, diabetes and periodontal disease, chronic pancreatitis, obesity, and a history of pancreatic cancer in first-degree relatives.
Researchers from the University of Illinois were looking for substances that would inhibit the development of cell lines of aggressive variants of this cancer and support treatment with chemotherapeutic drugs. To their surprise, they turned out to be flavonoids – apigenin and luteolin. They are found in abundance in common vegetables such as artichokes, celery and some herbs such as the Mexican variety of oregano.
Apigenin itself causes cell death in two aggressive human pancreatic cancer lines. We get the best results when we treat the tumor cells with apigenin for 24 hours and then give the chemotherapeutic drug gemcitabine for 36 hours – said Prof. Elvira de Mejia. As she added, the essence of apigenin treatment is its earlier administration before the chemotherapeutic agent. Dr Jodee Johnson working in the team of prof. de Meji claims that apigenin is a known antioxidant, and that administering it at the same time as the chemotherapeutic aborts the effect of this drug.
This is because one of the methods of chemotherapeutic drug killing cancer cells is pro-oxidative action, and apigenin is an antioxidant, so their effects can cancel each other out if it occurs at the same time, she added.
How does apigenin work
Apigenin works similarly to another flavonoid, also found in celery and artichoke – luteolin, which, however, is weaker. Both of these flavonoids trigger the production of the glycogenic kinase-synthesis enzyme 3β (GSK-3β). This enzyme is responsible for the decrease in the production of anti-apoptotic proteins in cancer cells. Apoptosis is programmed self-destruction of a cell due to DNA damage, so GSK-3ß simply activates a self-destructive mechanism in cancer cells.
The effect of apigenin is very visible – in the cancer cell line under study, apoptosis was 8,4%. After treating the cells with a dose of 50 micromoles of this flavonoid, the number of self-destructive cells increased to 43,8%. In this case, no chemotherapeutic agent was used afterwards. According to researchers from the team of prof. de Meji, the production of interleukin-17 is triggered in healthy pancreatic cells affected by apigenin. This cytokine is anti-inflammatory and prevents the spread of cancer cells.
Currently, scientists are working on the development of a drug containing therapeutic doses of apigenin. The dose contained in fresh or cooked vegetables is not enough to achieve an anti-cancer effect.
However, if people eat vegetables, fruits or herbs containing bioflavonoids, including apigenin, they will maintain their body concentration in such a way that they will significantly reduce the risk of cancer – said Prof. de Meji.
Bitter melon will help too
Meanwhile, researchers at the University of Colorado also published a paper pointing to flavonoids as a potential treatment for pancreatic cancer. A team of researchers from this university, led by Dr. Rajesh Agarwal, used an extract of cucumber balm (Momordica charantia L.) to destroy pancreatic cancer cells.
Cucumber balsam is a plant from the pumpkin family, with melon-like fruits, hence its English name – bitter melon, due to the bitter-sweet juice obtained from them. It is common in tropical and subtropical countries, and its juice is widely used in Asia. Traditional Chinese and Indian medicine indicated the cucumber balm. For centuries, products containing balm have been treated as a great remedy for type 2 diabetes. Chinese medicine saw in the balm also a remedy for pancreatic cancer, which Dr. Agarwal’s team decided to check.
In the course of the research, it was found that the lotion juice has a clear effect on the pathway of glucose metabolism in cells, which results in starvation of pancreatic cancer cells. Its active substance causes changes in the metabolism of cancer cells and the activation of AMP kinase, an enzyme that determines the low level of cellular energy, Dr. Agarwal told Science.
In the course of experiments carried out on a mouse model of pancreatic cancer, it turned out that in 60% of mice with cancer of this organ, fed with balsam juice, did not metastasize and develop the tumor. Scientists are currently working on isolating the active flavonoids from the lotion, responsible for the successful results of the experiment and the preparation of a working drug. This is more difficult than with apigenin, as there are probably two active flavonoids involved.
Cancer comes from inflammation
In turn, scientists from the Mayo Clinic have clarified an important issue – determining the relationship between chronic pancreatitis and pancreatic cancer. For practitioners, these two diseases are a huge clinical problem. They exhibit very similar symptoms, so there were misdiagnoses, and the symptoms characteristic of cancer manifested themselves when the therapy could no longer bring positive results.
A team led by biochemist Dr. Peter Storz found that during the inflammatory process, acinar cells in the pancreas that produce digestive enzymes turn into cells that resemble channel cells and begin to mutate so that it facilitates the development of cancer cells.
We don’t really know why these cells reprogram themselves. This is probably because the production of enzymes in an organ damaged by inflammation could further affect it. The good news, however, is that it can be reversed and we have identified the molecules involved in the process. In this way, we can turn the newly formed canal cells into acinar cells, eliminating the risk of cancer – said Dr. Storz
Dr. Storz’s team looked at the problem of transforming the inflammation of the pancreas into cancer. This process, as it turned out, took place when macrophages were active. Macrophages are derived from white blood cells and eliminate bacteria and harmful substances in the body. One macrophage can absorb up to 100 bacteria. In pancreatitis, macrophages did not replace dead cells, but facilitated the transformation of acinar cells into canal cells.
The entire transformation process was triggered by two enzymes. Scientists say they can serve as markers – their high concentration in the blood would indicate the onset of pancreatic cancer. Dr. Storz’s team is currently working on a rapid reversal of cell transformation – because if such a process can be stopped and changed, then macrophages, in accordance with their task, will help in the treatment of the inflammatory process, and will not play a negative role. According to scientists, the development of a drug in which bioflavonoids from, among others, from artichoke will last 2-3 years.
Tekst: Marek Mejssner