Authors
Young Jun Cho, Ki Young Choi, Soo-Min Byeon, Soyeon Kim, Kyung-Hee Pyo, Tae Won Kim, Seung Hwan Hong, Jung Weon Lee
Published in
BMB reports. Oct 21, 2026. Epub Oct 21, 2026.
Abstract
As a derivative of cyclic AMP (cAMP), 8-Chloro-cyclic AMP (8-Cl-cAMP) is shown to induce growth inhibition, apoptosis, and differentiation in different cancer cells by activating AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK). The p38 MAPK is known as a downstream mediator of 8-Cl-cAMP and binds to a multifunctional transcription factor Yin-Yang 1 (YY1). Although cytotoxic effects of 8-Cl-cAMP on cancer cells have been studied over several decades, molecular details or interplays by which they allow selective cytotoxicity to certain cancer cells remain unclear. Here, we further examined how YY1 expression could be affected by 8-Cl-cAMP treatment to understand the mechanism involved in cytotoxic effects of 8-Cl-cAMP on breast cancer cells. Treatment with 8-Cl-cAMP significantly decreased YY1 levels. Such decrease was reversed by co-treatment with ABT702, an adenosine kinase inhibitor. Moreover, pre-treatment with Compound C, an AMPK inhibitor, restored 8-Cl-cAMP-mediated decrease of YY1 expression, whereas SB203580 (a p38 MAPK inhibitor) did not. Meanwhile, siRNA against YY1 caused phosphorylation of p38 MAPK but not of AMPK, resulting in cell growth inhibition and cell death, as did 8-Cl-cAMP. These in vitro results suggest that 8-Cl- cAMP-mediated cytotoxicity might involve downregulations of YY1, which functions downstream of AMPK and upstream of p38 MAPK, and of ERα levels, supporting AMPK-YY1-p38 MAPK signaling axis in response to 8-Cl-cAMP. This study also indicates that 8-Cl-cAMP may have therapeutic potential against breast cancers expressing YY1 and ERα.
PMID:
42902568
Bibliographic data and abstract were imported from PubMed on 21 Oct 2026.
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