The research could help explain why some clinical studies have been unable to see a benefit of vitamin A on cancer: the vitamin does not appear to change the course of full-blown cancer, only pre-cancerous cells, and only works at a very narrow dose.
Since cells undergo many changes before they become fully aggressive and metastatic, Sandra V Fernandez, Assistant Research Professor of Medical Oncology at Thomas Jefferson University, and colleagues, used a model of breast cancer progression composed of four types of cells each one representing a different stage of breast cancer: normal, pre-cancerous, cancerous and a fully aggressive model.
Not only did the pre-cancerous cells begin to look more like normal cells in terms of their shape, they also changed their genetic signature back to normal.
The pre-cancerous cells had 443 genes that were either up or downregulated on their way to becoming cancerous. All of these genes returned to normal levels after treatment with retinoic acid.
"It looks like retinoic acid exerts effects on cancer cells in part via the modulation of the epigenome," said Fernandez.
The cells that were considered fully cancerous did not respond at all to retinoic acid, suggesting that there may be a small window of opportunity for retinoic acid to be helpful in preventing cancer progression.
In addition, the researchers showed that only one concentration of retinoic acid (about one micro Molar) produced the anti-cancer effects. Lower concentrations gave no change, and higher concentrations produced a smaller effect.
If those studies show the same effect, the next step would be to test whether these observations hold true in humans.
The research was published in the International Journal of Oncology.
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