24 Apr 2018 --- Acyclic retinoid, an artificial compound derived from vitamin A, may prevent the reoccurrence of liver cancer tumors. The vitamin A compound targets one common class of liver cancer cells, hepatocellular carcinoma (HCC), which are indicative of a highly lethal cancer with an extremely high rate of recurrence and relapse. The study proves how the acyclic retinoid can slow the growth of the cancer: by targeting levels of the dangerous MYCN in cells, this is true even amongst highly treatment-resilient “cancer stem cells.”

“We hope that in the near future, MYCN levels will be measured as a biomarker for judging the effectiveness of acyclic retinoid therapy, in the prevention of the recurrence of liver cancer,” Soichi Kojima, Ph.D, Professor and Unit Leader, Liver Cancer Prevention Research Unit, RIKEN Center for Integrative Medical Science, Japan, tells NutritionInsight.

Previous studies have found that acyclic retinoid was effective in stopping the recurrence of tumors. However, they were not sure as to why that was the case. Researchers in this study found that the expression of MYCN - a gene that is often found in tumors and is associated with poor life outcomes - was the key. They looked at the transcriptome of cells that had been exposed to acyclic retinoid, and found that compared to untreated cells, they had low expression of MYCN.

Further experiments, which involved deliberately repressing the appearance of the gene in cancer cells, showed that the reduction in MYCN led to slower cell progression, proliferation, and colony formation and to more cell death; essentially the acyclic retinoid on MYCN was slowing the cancer's growth.

Following this, the group focused on the role of “cancer stem cells”— cells that often survive the onslaught of chemotherapy treatment and often go on to divide and lead to reoccurrence of the cancer. They found, indeed, that high expression of MYCN was correlated with the expression of a number of markers that are associated with cancer stem cells.

Future applications
Cancer research is an on-going process, as a vast number of people are afflicted with the disease each year. Cancer is an extremely heterogenous sickness, of which its umbrella term comprises of 200 different conditions, according to Worldwide Cancer Research. Treatments that work for some cancers don’t work for others and sometimes those treatments simply stop working.

HCC is a particularly lethal cancer, which causes approximately 600,000 deaths each year around the world, making it the second deadliest cancer after non-small cell lung cancer. One of the reasons for the high lethality is that it has a high rate of recurrence – surgery and other treatments are initially effective, but the cancer then often relapses. This research could mark potential clinical treatment with MYCR levels being used a biomarker.

Moreover, the group hope to see a clinical treatment stemming from the research in a few years’ time, “We will start to explore the idea using patient data samples, and this will take one to two years for strong answers. Following this, the findings can hopefully be applied clinically.”

Kojima also points to a possibility that the method would work amongst other types of liver stem cells:

“The most interesting part of our finding,” says Kojima, “is when we then looked at different subpopulations of heterogeneous cancer cells. We found one specific group of EpCAM-positive cancer stem cells, where MYCN was elevated. We wondered if perhaps the key to acyclic retinoid’s effect was its ability to target these hepatic cancer stem cells. We also obtained similar results with CD133 positive liver cancer cells.”

Regarding the use of the treatment in other organ types, Kojima speculates that acyclic retinoid will indeed target MYCN similarly. However, for now, research is moving on to “studying a molecular mechanism(s) by which acyclic retinoid down-regulate the expression of MYCN at the transcriptional level through nuclear transglutaminase,” she concludes.

In related news that aligns nutrients and cancer, NutritionInsight has reported on the impact of biomarkers on the formation of colon cancer. In this case, researchers from Chalmers University of Technology, Sweden, found that two commonly used iron compounds – ferric citrate and ferric EDTA – increased the formation of a known biomarker – amphiregulin – for colon cancer, marking them as possibly carcinogenic properties. However, further research is needed.

By Laxmi Haigh

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