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AAT Bioquest

Midazolam Induces Cellular Apoptosis in Human Cancer Cells

One of the driving forces behind the scientific and technological revolution of the past few centuries has been the ability of scientists and other thinkers to apply known information to new situations. The ability to deduct a pattern from a series of occurrences, apply it to a new situation and then test its effectiveness has been the method of operation for rational science since its resurfacing several hundred years ago. This can be seen in full effect in the study conducted by Mishra et al. on the effects of Midazolam on human cancer. This compound, a γ-aminobutyric acid A (GABAA) receptor agonist, has been widely used as an anesthetic of the benzodiazepine class. However, recent attention paid to it has revealed that it has numerous other effects and that it can play a key role in the therapy of such diseases like cancer. For example, Midazolam has been found to induce neuronal cytotoxicity and apoptosis inducing activity in hematogenic, ectodermal, mesenchymal and neuronal cells. Because of this wide range of applications, Midazolam is a logical focus of study for potential cancer treatments.

Apoptosis induction is achieved in two ways: death receptor-dependent extrinsic or mitochondrial intrinsic. Midazolam does both in neuronal cells and has also shown calcium blocking principles in Jurkat cells. It also interferes with reactive oxygen species (ROS) generation and inhibits synthesis and release of nitric oxide and tumor necrosis factor α. The focus of this study was to test Midazolam in in vivo and in vitro colon cancer and leukemia to determine the effects in ROS production and to try and better understand cell death. One of the methods used to try and do this was to analyze mitochondria membrane potential using the fluorescent indicator JC-10™. This indicator is particularly useful in that it varies in color depending on excitation. This allows researchers to clearly identify changes in activity that might indicate the kind of cell death they are focusing on. This plus the improved signal to background ratio helps produce clear and reliable results that can be confidently used in the interpretation of the study's significance.

The results of this study indicated that Midazolam does indeed have a therapeutic effect on the processes in question and this offers support for the use of it in cancer mitigation. These types of advances are monumental for the medical community as it takes the field in general one step closer to developing safe and effective treatments for cancer, a disease that affects so many people worldwide. When dealing with such a sensitive topic of study, it is important that all results obtained are true and reliable. The JC-10™ indicator has improved solubility and a streamlined protocol that reduces hands-on time. All of this helps to improve its effectiveness in measuring mitochondrial membrane potential, which in turn reinforces the strength of the results and increases the validity of the study. It is important in medical research that a step forward never turns into a step backward; strong results and reliable experiments help make this happen and facilitate the advancement of the field.

 

References


  1. Mishra, Siddhartha Kumar, et al. "Midazolam induces cellular apoptosis in human cancer cells and inhibits tumor growth in xenograft mice." Molecules and cells 36.3 (2013): 219-226.


Original created on March 9, 2017, last updated on March 9, 2017
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