Activation of the Mitochondrial Apoptotic Pathway Produces Reactive Oxygen Species and Oxidative Damage in Hepatocytes That Contribute to Liver Tumorigenesis

Understanding how a particular disease develops is central to being able to determine a cure. This allows researchers to pinpoint the moment when the disease is most vulnerable and to develop treatments that target the specific biological process at work in its formation. This is one of the main challenges that researchers trying to determine potential therapies for Hepatocellular carcinoma (HCC). HCC is the 3^rd leading cause of cancer death in the world, and it tends to develop in patients that suffer from chronic hepatitis in any of its forms. What researchers do know about HCC is that high levels of serum alanine aminotransferase (ALT) is a risk factor for patients with chronic hepatitis because it can lead to the development of hepatocyte apoptosis. Since a recent study confirmed that hepatocyte apoptosis is indeed linked to the development of HCC—there was a lack of consensus for some time since apoptosis can also play a role in the destruction of cancer cells –a need has arisen to understand this process. Essentially, it has not been made clear how the activation of mitochondrial pathways of apoptosis leads to tumor development. This is what Hikita et al. set out to try and uncover with the hopes of better understanding HCC development and of revealing potential treatment options.

To do this Hikita and his team performed a series of in vitro and mitochondrial assays to try and better understand this process. What they found was that activation of mitochondrial pathways of apoptosis leads to the generation of Reactive Oxygen Species (ROS) without affecting the mitochondrial membrane potential. To measure the mitochondrial membrane potential, Hikita and his colleagues used the JC-10™ indicator. Its resistance to precipitation and greater signal to background ratio help produce clear and reliable results that allowed these researchers to see the real effects brought on by the activation of mitochondrial pathways. The JC-10™ indicator offers significantly enhanced signal intensity over previous indicators, allowing for more robust results that are easier to identify and more reliable.

The implications of this study reach beyond the simple pathology of HCC and extend into possible treatments. By being able to identify the generation of ROS as a key cause of HCC, a path towards treatment has been opened up. The present study suggests an anti-oxidant approach for people with chronic hepatitis to aid in the prevention of HCC. This proposal will surely need to be verified by further studies, but it offers a step in the right direction towards eradicating one of the leading causes of worldwide cancer death. When studying this cell behavior, researchers need to be overwhelmingly careful to not damage the sample they are examining. One way to do this is to use the JC-10™ indicator because it features an improved protocol for minimal hands-on time. This reduces user interference and helps to protect the integrity of the sample maintaining the reliability of the results and the ultimate validity of the study.

References

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1. Hayato Hikita, Takahiro Kodama, Satoshi Tanaka, Yoshinobu Saito, Yasutoshi Nozaki, Tasuku Nakabori, Satoshi Shimizu, Yoshito Hayashi, Wei Li, Minoru Shigekawa, Ryotaro Sakamori, Takuya Miyagi, Naoki Hiramatsu, Tomohide Tatsumi and Tetsuo Takehara. Activation of the Mitochondrial Apoptotic Pathway Produces Reactive Oxygen Species and Oxidative Damage in Hepatocytes That Contribute to Liver Tumorigenesis Cancer Prevention Research (2015), DOI: 10.1158/1940-6207.CAPR-15-0022-T Published August 2015