A3 adenosine receptor as a target for cancer therapy

被引:116
作者
Fishman, P [1 ]
Bar-Yehuda, S
Madi, L
Cohn, I
机构
[1] Tel Aviv Univ, Rabin Med Ctr, Felsenstein Med Res Ctr, Lab Tumor & Clin Immunol, IL-49100 Petah Tiqwa, Israel
[2] Can Fite Biopharma, IL-49160 Petah Tiqwa, Israel
关键词
A3 adenosine receptor; adenosine; cancer therapy; myeloprotection;
D O I
10.1097/00001813-200206000-00001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Targeting the A3 adenosine receptor (A3AR) by adenosine or a synthetic agonist to this receptor (IB-MECA and CI-IB-MECA) results in a differential effect on tumor and on normal cells Both the adenosine and the agonists inhibit the growth of various tumor cell types such as melanoma, colon or prostate carcinoma and lymphoma. This effect is specific and is exerted on tumor cells only. Moreover, exposure of peripheral blood mononuclear cells to adenosine or the agonists leads to the induction of granulocyte colony stimulating factor (G-CSF) production. When given orally to mice, the agonists suppress the growth of melanoma, colon and prostate carcinoma in these animals, while inducing a myeloprotective effect via the induction of G-CSF production. The de-regulation of the Wnt signaling pathway was found to be involved in the anticancer effect. Receptor activation induces inhibition of adenylyl cyclase with a subsequent decrease in the level of protein kinase A and protein kinase B/Akt leading to activation of glycogen synthase kinase-3beta, a key element in the Wnt pathway. The oral bioavailability of the synthetic A3AR agonists, and their induced systemic anticancer and myeloprotective effect, renders them potentially useful in three different modes of treatment: as a stand-alone anticancer treatment, in combination with chemotherapy to enhance its therapeutic index and myelprotection. It is evident that use of the A3AR agonist for increasing the therapeutic index of chemotherapy may also invariably give rise to myeloprotection and vice versa. The A3AR agonists are thus a promising new class of agents for caner therapy. [(C) 2002 Lippincott Williams Wilkins.].
引用
收藏
页码:437 / 443
页数:7
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