HAYWARD, Calif., May 16, 2018 (GLOBE NEWSWIRE) -- A discovery made using Phenotype MicroArray™ technology has led to a deeper understanding of the lethal role of the PTEN null mutation in prostate cancer while also suggesting a new avenue for treatment. The breakthrough work was published in the latest issue of the journal Cell Reports by Lloyd Trotman and coworkers at the Cold Spring Harbor Laboratory.
The project evolved from an initial observation made in 2011 when the Trotman laboratory was making an evaluation of Biolog's technology. They created two cell lines that differed only by the PTEN null mutation and then, in a simple experiment, they compared the sensitivity of the cells by phenotypic assay using Biolog’s panel of 92 chemicals with anti-cancer capabilities. The PTEN null cells, which model a lethal form of prostate cancer, exhibited a 27-fold increase in sensitivity to killing by two similar chemicals, rotenone and deguelin, known to inhibit mitochondrial complex 1. This observation pointed clearly to the mitochondria as the vulnerable site in the prostate cancer cells.
Mitochondria are organelles inside of human and other eukaryotic cells that produce most of the energy that cells need to survive and grow. They are very complex and are coded for by more than 1100 genes that are dynamically regulated. When different cell types have mitochondrial defects, it can lead to wide ranging energetics-related disorders including cancer and ageing, neurological disorders, metabolic disorders, and immuno-deficiencies. To elucidate the connection between the PTEN null mutation and defective mitochondrial function, Trotman collaborated with a mitochondrial expert at Northwestern Medical School, Navdeep Chandel, and ultimately discovered that the cancer cells were using mitochondrial complex 5 to consume rather than produce ATP.
These discoveries have found a potential Achilles heel of the deadly prostate cancer cells. Studies on mice with endogenous PTEN null prostate cancer showed successful treatment with deguelin. Newer efforts toward human studies are being undertaken with another complex 1 inhibiting drug, metformin, which has an excellent safety profile and is a mainstay drug for treating type 2 diabetes.
“Biolog’s Phenotype MicroArray technology provided the original breakthrough for us,” said Dr. Trotman. “That single and simple experiment pointed the direction for us and got us going down the road. It has taken us several years to understand why rotenone and deguelin are so selective, but we were confident in moving forward because we saw that the Biolog results were extremely robust.”
In those intervening years, Biolog has continued to innovate and develop more cell assay technologies to support and enable groundbreaking discoveries. According to Barry Bochner, Biolog’s CEO, “our company has recently introduced a new MitoPlate™ product line that adds a major new capability to Biolog’s existing Phenotype MicroArray™ product line. The new product line consists of two testing panels that can measure more than 50 properties of human cell mitochondria. These, as well as the Phenotype MicroArray assays, can all be read on Biolog’s versatile OmniLog® instrument. Product information and details about the MitoPlates can be found at: http://www.biolog.com/products-static/mitochondrial_function_assays.php
About Biolog, Inc.
Biolog is a privately held company based in Hayward, CA, that continues to lead in the development of powerful new cell analysis tools for solving critical problems in biological, pharmaceutical, and biotechnological research and development. It is the world leader in phenotypic cell profiling. Biolog products are available worldwide, either directly from the company or through its extensive network of international distributors. Further information can be obtained at Biolog's website, www.biolog.com.
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