Adenosine A1 receptor modifies P53 expression and apoptosis in breast cancer cell line Mcf-7

Abstract

BACKGROUND: Breast cancer cells over-express the adenosine receptor A1 and in most of these cells, P53 gene is a wild type. Because of this fi nding and relationship between A1 receptor and cell apoptosis and proliferation, this study aimed to determine the effect of agonist and antagonist of A1 receptor on cell apoptosis and proliferation and recognize the relationship between this receptor and P53 expression. METHODS: We used a Real-Time PCR test for measuring expression of p53 gene also fl ow cytometry assay for apoptotic and survival cell rate after treatment of MCF-7 cells with A1 receptor agonist CPA (N6-Cyclopentyladenosine) and A1 receptor antagonist DPCPX (1,3-dipropyl-8-cyclopentylxanthine) in 24,48 and 72 hours. RESULTS: Our fl ow cytometry fi ndings indicate that DPCPX signifi cantly induces apoptosis in MCF-7. Also the expression of P53 becomes upregulated with time of DPCPX treatment. CPA treatment increased the survival cell rate and down-regulated this apoptosis-relevant gene P53 (p > 0.05). CONCLUSION: DPCPX can induce P53 expression which consequently promotes the cell apoptosis in MCF-7. Therefore, DPCPX could be used as an anti-cancer agent (Tab. 1, Fig. 3, Ref. 5). Text in PDF www.elis.sk.

Cordycepin induces apoptosis in human liver cancer HepG2 cells through extrinsic and intrinsic signaling pathways

“…It has been shown that cordycepin is an analogue of adenosine (22). The possibility that the adenosine receptor is involved in the apoptosis of certain types of cancer cells, including ovarian (38), breast (39) and renal (40) cancer cells, has also been proposed. Thus, additional studies investigating whether cordycepin induces apoptosis through adenosine receptors in HepG2 cells may be valuable.…”

Role of adenosine signaling in the pathogenesis of head and neck cancer

“…The antitumor activity of A3AR agonists is attributed to stimulating natural killer cells, which increases eradication of cancer cells. It has also been demonstrated that treatment of MCF‐7 breast cancer cells with 1,3‐dipropyl‐8‐cyclopentylxanthine, an A1AR antagonist, significantly increases p53 expression, enhancing apoptosis, whereas administration of N6‐cyclopentyladenosine, an A1AR agonist, induces cell survival and inhibits apoptosis by downregulating p53 expression . Consistent with the regulatory effect of ARs on apoptosis, Mediavilla‐Varela et al have shown that suppression of A2aAR by A2AaR antagonists including ZM241385 and SCH58261 elicits anticancer effects by inhibiting tumor growth in tumor xenograft progression in mice.…”

“…It has also been demonstrated that treatment of MCF-7 breast cancer cells with 1,3-dipropyl-8-cyclopentylxanthine, an A1AR antagonist, significantly increases p53 expression, enhancing apoptosis, whereas administration of N6-cyclopentyladenosine, an A1AR agonist, induces cell survival and inhibits apoptosis by downregulating p53 expression. 36 Consistent with the regulatory effect of ARs on apoptosis, Mediavilla-Varela et al 37 have shown that suppression of A2aAR by A2AaR antagonists including ZM241385 and SCH58261 elicits anticancer effects by inhibiting tumor growth in tumor xenograft progression in mice. Cekic et al 38 reported that intratumor injection of aminophylline, a nonselective AR antagonist, and ATL801, a selective A2bAR antagonist, significantly elevated levels of interferon-γ (IFN-γ) Iand IFN-stimulating chemokine CXCL10 in bladder and breast tumors.…”

Therapeutic potency of pharmacological adenosine receptors agonist/antagonist on cancer cell apoptosis in tumor microenvironment, current status, and perspectives

“…Similarly, downregulation of A1AR using small interfering RNA (siRNA), induces apoptosis in MDA‐MB‐468 cells (Mirza et al, ). In another study Dastjerdi et al () showed that treatment of breast cancer cells, MCF‐7, with n6‐Cyclopentyladenosine (CPA), an A1AR agonist, decreases apoptosis whereas stimulation of these cells with 1, 3‐dipropyl‐8‐cyclopentylxanthine (DPCPX), an A1AR antagonist, enhances cell apoptosis by upregulating pro‐apoptotic factors including p53, caspases‐3, 8, and 9 (Dastjerdi, Rarani, Valiani, & Mahmoudieh, ; Dastjerdi, Valiani, Mardani, & Ra, ).…”