The Differential Antitumor Activity of 5-Aza-2'-deoxycytidine in Prostate Cancer DU145, 22RV1, and LNCaP Cells

Abstract

DNA methylation is a DNA methyltransferase-mediated epigenetic modification affecting gene expression. This process is involved in the initiation and development of malignant disease. 5‐Aza‐2′‐deoxycytidine (5‐Aza), a classic DNA methyltransferase inhibitor, possesses antitumor proliferation activity. However, whether 5-Aza induces cytotoxicity in solid tumors warrants further investigated. In this study, human prostate cancer (CaP) cells were treated with 5-Aza and subjected to cell viability and cytotoxicity analysis. Reverse transcription-polymerase chain reaction and methylation-specific polymerase chain reaction assay were utilized to test the gene expression and methylation status of the p53 and p21 gene promoters. The results showed that 5-Aza differentially inhibited spontaneous proliferation, arrested the cell cycle at S phase in DU145, at G1 phase in 22RV1 and LNCaP cells, and G2 phase in normal RWPE-1 cells, as well as induced the expression of phospho-H2A.X and tumor suppressive mammary serine protease inhibitor (maspin) in all three types of CaP cells. 5-Aza also increased p53 and p21 transcription through promoter demethylation, and decreased the expression of oncogene c-Myc in 22RV1 and LNCaP cells. Western blotting analysis showed that the poly (ADP-ribose) polymerase cleavage was detected in DU145 and 22RV1 cells. Moreover, there were no significant changes in p53, p21 and c-Myc expression in DU145 cells following treatment with 5-Aza. Thus, in responsible for its apoptotic induction and DNA damage, the mechanism of the antitumor activities of 5-Aza may involve in an increase of tumor suppressive maspin, upregulation of wild type p53-mediated p21 expression and a decrease of oncogene c-Myc level in 22RV1 and LNCaP cells, and enhancing the tumor suppressive maspin expression in DU145 cells. These results enriched our understanding of the multifaceted antitumor activity of 5-Aza, and provided the expression basis of biomarkers for its possible clinical application in prostate cancer.

Promoter Gene Methylation Regulates Clooxygenase-2 Expression in Androgen-Dependent and Independent Prostate Cancer Cells

“…6 ). These results were consistent with the findings of Cheng et al [ 36 ]. We will investigate the functions of DNMT inhibitor in prostate cancer by using in vivo models in the future.…”

Dysregulation of the miRNome unveils a crosstalk between obesity and prostate cancer: miR-107 asa personalized diagnostic and therapeutic tool

“…These results obtained from androgen-dependent versus androgen-independent PCa cells have not been reported before and suggest the idea that miR-107 could play a different endogenous role in PCa cells, depending on the degree of tumor aggressiveness, maybe due to the sophisticated molecular mechanism of regulation of miRNAs in different cell types. 5 Therefore, although differential responses in androgendependent versus androgen-independent PCa cells have been previously reported, [32][33][34] this particular phenomenon observed in our study warrants further investigation in order to unveil its clinical implication.…”

FAM107A Inactivation Associated with Promoter Methylation Affects Prostate Cancer Progression through the FAK/PI3K/AKT Pathway

“…In this study, the expression of FAM107A in DU 145 and PC 3 cell lines was restored to some extent by treating prostate cancer cells with the demethylating drug 5-Aza [ 23 ] or by knocking down the expression of DNMT1 in siDNMT1 cells. This finding is in agreement with a previous report by Donkena et al [ 24 ].…”