Biochemical and Biophysical Research Communications
Histone deacetylase inhibitor, Trichostatin A, activates p21WAF1/CIP1 expression through downregulation of c-myc and release of the repression of c-myc from the promoter in human cervical cancer cells
Section snippets
Materials and methods
Cell line and reagents. Human cervical carcinoma cells (HeLa) were maintained in Dulbecco’s modified Eagle’s medium (DMEM), supplemented with 10% fetal bovine serum (Hyclone), 1% penicillin, and streptomycin (Invitrogen). Trichostatin A (Sigma) was dissolved in dimethyl sulphoxide (DMSO).
Reverse transcription and polymerase chain reaction. Total cellular RNA was isolated with TRIzol reagent (Invitrogen) and DNAs were removed with DNA-free kit (Ambion) according to the manufacturer’s
TSA induces morphological changes of HeLa cells
HeLa is an epithelia-like cervical carcinoma cell line which contains human papillomavirus type 18. HeLa cells are normally oval or polygonal, with few cells showing elongation (Fig. 1A). However, treatment with 100 nM TSA for 16 h resulted in characteristic elongated cells with filamentous protrusions (Fig. 1B). These changes in morphology resemble cells that have undergone replicative senescence, cell cycle arrest, and/or apoptosis [19], [7].
TSA-induced p21WAF1/CIP1 expression correlates with downregulation of c-myc in HeLa cells
The induction of p21WAF1/CIP1 is one of the common
Discussion
In the current study, we found that HeLa cells appeared to undergo morphological changes after TSA treatment for 16 h, which were consistent with morphology of the cells that have undergone replicative senescence, cell arrest, and/or apoptosis [19], [7]. Thus, TSA is highly effective in suppressing the growth of HeLa cells. Expression of p21WAF1/CIP1, a cyclin-dependent kinase inhibitor which has an important role in arresting the cell cycle in the G1 phase, is likely to account for this effect.
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2014, FEBS LettersCitation Excerpt :For example, SP1 upregulates p21 expression in p53-null Caco-2 cells derived from human colon carcinoma [5]. In addition, transcription factors such as ataxia telangiectasia-mutated (ATM), c-Myc, breast cancer 1, early onset (BRCA1), and Kruppel-like factor 6 (KLF6) can regulate the cell cycle and suppress cell growth by activating p21 transcription even in the absence of p53 [6–9]. Checkpoint kinase 2 (Chk2)-dependent induction of p21 transcription occurs in p53-defective breast carcinoma SK-BR-3 and HaCaT cells [10].
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