This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chung, H. Articles by Kong, G. Search for Related Content PubMed PubMed Citation Articles by Chung, H. Articles by Kong, G.

¹ Department of Pathology, College of Medicine, Hanyang University and ² Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Woman's University, Seoul, Republic of Korea

Requests for reprints: Gu Kong, Department of Pathology, College of Medicine, Hanyang University, 133-791 Seoul, Republic of Korea. Phone: 82-2-2290-8251; Fax: 82-2-2295-1091. E-mail: gkong{at}hanyang.ac.kr

Agonists to A3 adenosine receptor (A3AR) have been reported to inhibit cell growth and/or induce apoptosis in various tumors. We tested the effect of a novel A3AR agonist generically known as LJ-529 in breast cancer cells. Anchorage-dependent cell growth and in vivo tumor growth were attenuated by LJ-529, independently of its estrogen receptor (ER) status. In addition, apoptosis was induced as evidenced by the activation of caspase-3 and c–poly(ADP)ribose polymerase. Furthermore, the Wnt signaling pathway was down-regulated and p27^kip was induced by LJ-529. In ER-positive cells, the expression of ER was down-regulated by LJ-529, which might have additionally contributed to attenuated cell proliferation. In ER-negative, c-ErbB2-overexpressing SK-BR-3 cells, the expression of c-ErbB2 and its downstream extracellular signal-regulated kinase pathway were down-regulated by LJ-529. However, such effect of LJ-529 acted independently of its receptor because no A3AR was detected by reverse transcription-PCR in all four cell lines tested. In conclusion, our novel findings open the possibility of LJ-529 as an effective therapeutic agent against both ER-positive and ER-negative breast cancers, particularly against the more aggressive ER-negative, c-ErbB2-overexpressing types. [Mol Cancer Ther 2006;5(3):685–92]

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7/14/05; revised 12/ 8/05; accepted 1/11/06.