8-Chloroadenosine 3',5'-monophosphate induces cell cycle arrest and apoptosis in multiple myeloma cells through multiple mechanisms

Cheng,Yi-Min; Zhu,Qi; Yao,Yi-Yun; Tang,Yong; Wang,Ming-Ming; Zou,Li-Fang

doi:10.3892/ol.2012.905

8-Chloroadenosine 3',5'-monophosphate induces cell cycle arrest and apoptosis in multiple myeloma cells through multiple mechanisms

Authors:
- Yi-Min Cheng
- Qi Zhu
- Yi-Yun Yao
- Yong Tang
- Ming-Ming Wang
- Li-Fang Zou
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Affiliations: Department of Hematology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
Published online on: September 11, 2012 https://doi.org/10.3892/ol.2012.905
Pages: 1384-1388

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Abstract

The aim of this study was to investigate the molecular mechanism of 8-chloroadenosine 3',5'-monophosphate (8-Cl‑cAMP) in the inhibition of the growth and induction of apoptosis of multiple myeloma (MM) cells. Two MM-derived cell lines, RPMI-8226 and U266, were used. Cell viability, apoptosis induction and mitochondrial transmembrane potential were determined and the expression levels of cell cycle regulatory proteins (Cdk2, cyclin E, p27 and c-myc) and p38 mitogen‑activated protein kinase (MAPK) protein were detected. Following treatment with 8-Cl-cAMP, the percentage of apoptotic cells increased in a concentration- and time-dependent manner and the mitochondrial transmembrane potential collapsed to reveal typical apoptotic features. Our data further demonstrated that 8-Cl-cAMP induced progressive phosphorylation of p38 MAPK and that the expression levels of p27 proteins in the MM cells were increased whereas those of c-myc were significantly decreased. Notably, the pro-apoptotic effect of 8-Cl-cAMP was largely prevented by a p38 MAPK inhibitor. Furthermore, knockdown of p27 was able to decrease the 8-Cl-cAMP-induced apoptosis in the MM cells. These results indicate that 8-Cl‑cAMP induced p27-dependent cell cycle arrest and apoptosis in the MM cells, which demonstrates the potential of cAMP-modulating agents for use in the treatment of MM.

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