Identification of an Annonaceous Acetogenin Mimetic, AA005, as an AMPK Activator and Autophagy Inducer in Colon Cancer Cells

Perhaps the greatest challenge facing the medical community today is the search for a cure for cancer. It comes in so many forms, and affects the lives of so many people, that, rightly so, there has been an outpouring of support for the research and development of effective cancer therapies. There has been some modest success in some areas, but much work is still to be done. And even when there appears to be success, further research is needed to understand why there was success in the first place, so that the safety and repeatability of the therapy can be confirmed. For example, annonaceous acetogenins, a large family of naturally occurring polyketides coming from the plant genus Annonaceae, have been shown to be rather effective at killing a variety of cancer cells. However, the underlying mechanisms as to why this occurs remain somewhat of a mystery to the cancer research community. Some studies have indicated that these compounds could be acting on the mitochondria complex-I, blocking the corresponding electron transport chain and terminating ATP production. However, this is about the extent of what is known.

The focus of the study conducted by Liu et al. from the Graduate University of the Chinese Acadamy of the Sciences was to test out a variety of different annonaceous acetogenins, pitting their potency against different types of cancer cells to understand what causes these reactions. One of the ways to do this is to measure the activity of ubiquione-linked NADH oxidase, since annonaceous acetogenins have been shown to disrupt this as well as mitochondrial function I, by binding the third loop of the ND1 subunit in mitochondrial NADH-ubiquinone oxidoreductase. To perform this part of the experiment, Liu's team made use of the Amplite Fluorimetric Total NAD and NADH Assay Kit. The reason for this choice is that this assay kit has been proven to be far more accurate and sensitive than other assay kits of its kind. It does this by making use of a different measurement method than most other assay kits. Instead of relying on monitoring the NAD or NADPH absorption, it uses enzymes and an enzyme cycling reaction to specifically recognize NAD/NADH, meaning higher sensitivity and better accuracy. The assay has demonstrated high sensitivity and low interference with 570 nm excitation 590 nm emission.

Overall, the results of this study indicate that a mimetic AA005 can be significantly effective in inducing cycle cell arrest followed by autophagy, suggesting it has real promise to be an effective therapy for some cancers. This is a major breakthrough, as it helps outline a specific treatment while also shedding light on some of the reasons why it is successful. For this study to be successful, the research team needed to carefully monitor NAD/NADH activity in the mitochondria, and they were able to do this through the use of the Amplite Fluorimetric Total NAD and NADH Assay Kit. Without tools like this, it would be much harder to make the sound conclusions needed to help push the research frontier closer to finding a cure for cancer.

References

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1. Liu, Yong-Qiang, et al. "Identification of an annonaceous acetogenin mimetic, AA005, as an AMPK activator and autophagy inducer in colon cancer cells." PloS one 7.10 (2012): e47049.