SHIRLEY, NOV 30TH,2017 - Researchers from the Albert Einstein College of Medicine found a compound that can directly contribute to the "suicide" of cancer cells for the first time by inducing cell apoptosis, moreover, it will not affect specific compounds in healthy cells of the body. The study results was published in the Journal of Cancer. As a new type of therapy which can directly resist Acute Myeloid Leukemia (AML) cells, it also can help offer effectively supply for other types of cancer cells.
Professor Evripidis Gavathiotis, one of the researchers for this study, claimed that this new targeting compounds they developed were more effective than the current anticancer therapies, which promote cancer cells to self-destruct. Ideally, this new type of compounds will work with other therapies to kill cancer cells more quickly and efficiently but with fewer side effects, while the traditional chemotherapy often causes some side effects to patients.
AML, which accounts for almost a third of all new forms of leukemia, causing more than 10,000 deaths each year in the United States. The survival rate of AML patients has remained at about 30% for decades, that’s why researchers devote to developing better therapies. In this study, researchers discovered that new compounds help fight cancer effectively by inducing cell apoptosis, which can "trim" extra tissue during embryonic development and some chemotherapeutic drugs can induce cell apoptosis indirectly by damaging the DNA of cancer cells.
While a protein called BAX in the cells is activated by a pro-apoptotic protein, it will trigger cell apoptosis. BAX molecules automatically navigate and cause fatal "holes" in the mitochondria. However, cancer cells generally try to inhibit the killing effect of BAX protein, which can suppress the BAX protein and activate the special protein of BAX molecule by generating a large number of anti-apoptotic proteins so as to keep the cancer cells surviving.
In 2008, Gavathiotis first described the shape and structure of the BAX protein activation site in an article published in Nature. Researchers detected some small molecules that could activate BAX protein to overcome cancer tolerance to cell apoptosis. At first, they ultilized computers to screen more than one million compounds to find out which compounds involve the binding properties of BAX, then test and evaluate the 500 filtered out compunds in the laboratory.
The researchers showed that the compound named BTSA1 (BAX Trigger Site Activator 1) is the most potential activator of BAX. While being added to a number of different human AML cell lines, BTSA1 is able to elicit a rapid and extensive apoptotic effect. Furthermore, Researchers will test BTSA1 in blood samples from high-risk AML patients, and it is clear that BTSA1 can induce apoptosis in cells of AML patients without affecting healthy blood-forming stem cells in the body.
Researchers created human AML animal models by implanting human AML cells into the body of a mouse. The BTSA1 compound was then administered to half of AML mice and the other half to the control. The results showed that the survival of mice treated with BTSA1 was significantly prolonged (55 days) compared to the control mice (40 days), 43% of of BTSA1-treated AML mice survived more than 60 days without any signs of AML disease.
More importantly, there is no evidence of toxicity was found in the mice treated with BTSA1, it can activate the BAX protein and trigger cell apoptosis in AML cells without damaging healthy cells and tissues, primarily because cancer cells are already prepared for apoptosis. The researchers said that AML cells from the patients contain higher levels of BAX protein than normal blood cells in healthy human body. Moreover, more AML cells will accumulate BAX protein accumulation, and even low levels of BTSA1 can induce enough BAX activation to induce apoptosis in cancer cells. What’s more, it will not produce any damaging effects on the healthy cells that contain low levels of BAX or no BAX protein.
For the further development of this study, researchers will look through more in-depth cell based assay studies to figure out if BTSA1 has a similar therapeutic effect on animal models of other types of cancer.
About the cell apoptosis assay offered by Creative Bioarray
Creative Bioarray provides Cell Apoptosis Assays to all of our customers. The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer.
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