With the continuous research on epigenetics, it has been recognized that abnormal epigenetic modifications of cells play an important role in tumorigenesis. Histone acetylation is one of the most important modifications occurring in cells. Generally, most of the histones in cancer cells show low acetylation status. However, HDACis could regulate and inhibit the process of histone deacetylation. Therefore, more and more HDACis as the new anticancer agents have been developed and applied to cancer treatment. TSA as one of the typical representative drugs of HDACis could suppress the enzymatic activity of deacytylases to promote the acetylation level of both histone and nonhistone proteins in cells. However, the mechanism of TSA affecting cancer cells has not been well understood. Moreover, how to monitor rapidly and analyze quantitatively the processes of TSA on cells is another important challenge.
To address this issue, Professor Huang’s group employed the advanced spectroscopic tools to study various physical and chemical processes and changes of cellular structures and components in organisms for long time. Compared to traditional methods, Fourier transform infrared (FTIR) spectroscopy has some special advantages such as simple operation, rapid detection, and non-destructive measurement. In the reported work, they employed FTIR spectroscopy together with fluorescence imaging technique to probe the effect of TSA on HeLa cells, and especially scrutinized the physicochemical changes of cytoskeletons in cells treated with TSA by analyzing the FTIR data obtained under different conditions. Their results showed that TSA caused elevated level of cellular acetylation and conformation/structural changes of proteins in cells, and higher dosage of TSA caused higher percent of α-helix structure accompanied by increment of acetylation level in both histones and cytoskeleton proteins.
This work therefore not only validates the usefulness of FTIR spectroscopy in the quantitative assessment of cellular acetylation, but also may open an avenue to the in-depth investigation of the effect of HDAC inhibitor drugs such as TSA on cancer cells. The work has been accepted by Analytical Chemistry (DOI: 10.1021/ac504691q).
