HDAC Inhibitor TSA Induces Cell Death and Morphological Changes in Cervical Cancer Cells

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2020-09-29

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Cervical cancer is the third leading cause of cancer deaths in women worldwide. While human papillomavirus (HPV) is necessary for cervical cancer, it is not sufficient. Other genetic and/or epigenetic changes likely contribute to cervical carcinogenesis. Trichostatin A (TSA) is a histone deacetylase (HDAC) inhibitor known to inhibit proliferation and promote apoptosis in multiple cancer cells. However, its anti-cancer effects in cervical squamous cell carcinoma, the most frequent type of cervical malignancy, have not yet been elucidated. We examined the effect of TSA on several cervical cancer cell lines by treating them with TSA for up to 4 days. We used both HPV+ (SiHa, Caski, and MS751) and HPV- (c33a) cervical cancer cells. TSA (50-150 nM) significantly decreased the number of cells in cell counting and crystal violet-staining assays. Compared to vehicle, cells treated with 100 nM TSA decreased to 12% in Caski, 26% in SiHa, 41% in MS751, and 0.03% in c33a. Although some of these experiments need to be repeated for statistical analyses, our data suggest that TSA induces cell death and/or inhibits proliferation in cervical cancer cells regardless of the HPV status. Additionally, cervical cancer cells treated with TSA became elongated and had more protrusions compared to control cells, raising the possibility that TSA induces epithelial-mesenchymal transition (EMT) in cervical cancer cells. To develop this further, we will identify which HDAC is responsible for survival and proliferation. We anticipate that further study will shed new light on the role of epigenetic regulation in cervical cancer.

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