Clofarabine Has Apoptotic Effect on T47D Breast Cancer Cell Line via P53R2 Gene Expression

Rahmati-Yamchi, Mohammad; Zarghami, Nosratollah; Charoudeh, Hojjatollah Nozad; Ahmadi, Yasin; Baradaran, Behzad; Khalaj‐Kondori, Mohammad; Milani, Morteza; Akbarzadeh, Abolfazl; Shaker, Maghsud; Pourhassan‐Moghaddam, Mohammad

doi:10.15171/apb.2015.064

Cited by 7 publications

(2 citation statements)

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“…Moreover, ClF-induced apoptosis has been demonstrated in other types of cancer. Rahmati-Yamchi and others (Rahmati-Yamchi et al, 2015) reported that ClF has an apoptotic effect on the T47D breast cancer cells via regulation of P53R2 gene expression in a time-and dose-dependent manner. In the Wang and Albertioni's studies, exposure of human HCT116 epithelial colon cancer cells to ClF has caused a rapid reduction in thymidine incorporation into DNA during DNA synthesis and a 3-fold increase in apoptosis induction (Wang & Albertioni, 2010).…”

Section: Clf Inhibits Cell Growth and Induces Apoptosis In All Cellsmentioning

confidence: 96%

“…ClF has demonstrated cytotoxicity to a variety of human hematologic and solid tumor cell lines and tumor xenograft models (the leukemia, colon, and breast tumor models) (Takahashi et al, 2002;Majda et al, 2010;Wang & Albertioni, 2010;Lubecka-Pietruszewska et al, 2014;Yamauchi et al, 2014;Rahmati-Yamchi et al, 2015;Stumpel et al, 2015). Although the mechanisms of ClF cytotoxic activity (the antiproliferative and proapoptotic effects) have been extensively studied in ALL in vitro and in vivo models, almost nothing is known about ClF possible role as a hypomethylating agent in ALL inhibition.…”

Section: Introductionmentioning

confidence: 99%

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The effects of clofarabine in ALL inhibition through DNA methylation regulation

Kaufman‐Szymczyk

Lubecka

2020

Acta Biochim Pol

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Clofarabine (2-chloro-2’-fluoro-2’-deoxyarabinosyladenine, ClF), a second-generation 2’-deoxyadenosine analog, possesses manifold anti-cancer activities. Our previous reports and some of others demonstrate the potential capacity of ClF to regulate the epigenetic machinery. The study presented here is the first to investigate the influence of ClF on modulators of the DNA methylation machinery, including DNMT1 and CDKN1A, in acute lymphoblastic leukemia (ALL) cells. ClF effects on promoter methylation and transcriptional activity of hypermethylated and silenced tumor suppressor genes (TSGs), including APC, CDKN2A, PTEN, and RARB, have been tested as well. Methylation level of the proximal promoter region of APC, CDKN2A, PTEN, and RARB, as well as expression of those TSGs, DNMT1 and CDKN1A, were estimated by using a methylation-sensitive restriction analysis and qPCR, respectively. The Nalm-6 cell line was used as an experimental in vitro model of ALL cells. We observed ClF-mediated inhibition of cellular viability and apoptosis induction of Nalm-6 cells with an increased percentage of cells positive for active Caspase-3. Interestingly, exposure of Nalm-6 cells to CIF at 20 nM concentration for three days has led to a significant DNMT1 downregulation, accompanied by robust CDKN1A upregulation. ClF caused hypomethylation of APC, CDKN2A, and PTEN, with a concomitant increase in their transcript levels. Taken together, our results demonstrate the ability of ClF to reactivate DNA methylation-silenced TSGs in ALL cells. This may implicate translational significance of our findings and support ClF application as a new epigenetic modulator in the anti-leukemia therapy.

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Section: Clf Inhibits Cell Growth and Induces Apoptosis In All Cellsmentioning

confidence: 96%