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Article

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
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
  • Pages: 1384-1388
    |
    Published online on: September 11, 2012
       https://doi.org/10.3892/ol.2012.905
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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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Copy and paste a formatted citation
Spandidos Publications style
Cheng Y, Zhu Q, Yao Y, Tang Y, Wang M and Zou L: 8-Chloroadenosine 3',5'-monophosphate induces cell cycle arrest and apoptosis in multiple myeloma cells through multiple mechanisms. Oncol Lett 4: 1384-1388, 2012.
APA
Cheng, Y., Zhu, Q., Yao, Y., Tang, Y., Wang, M., & Zou, L. (2012). 8-Chloroadenosine 3',5'-monophosphate induces cell cycle arrest and apoptosis in multiple myeloma cells through multiple mechanisms. Oncology Letters, 4, 1384-1388. https://doi.org/10.3892/ol.2012.905
MLA
Cheng, Y., Zhu, Q., Yao, Y., Tang, Y., Wang, M., Zou, L."8-Chloroadenosine 3',5'-monophosphate induces cell cycle arrest and apoptosis in multiple myeloma cells through multiple mechanisms". Oncology Letters 4.6 (2012): 1384-1388.
Chicago
Cheng, Y., Zhu, Q., Yao, Y., Tang, Y., Wang, M., Zou, L."8-Chloroadenosine 3',5'-monophosphate induces cell cycle arrest and apoptosis in multiple myeloma cells through multiple mechanisms". Oncology Letters 4, no. 6 (2012): 1384-1388. https://doi.org/10.3892/ol.2012.905
Copy and paste a formatted citation
x
Spandidos Publications style
Cheng Y, Zhu Q, Yao Y, Tang Y, Wang M and Zou L: 8-Chloroadenosine 3',5'-monophosphate induces cell cycle arrest and apoptosis in multiple myeloma cells through multiple mechanisms. Oncol Lett 4: 1384-1388, 2012.
APA
Cheng, Y., Zhu, Q., Yao, Y., Tang, Y., Wang, M., & Zou, L. (2012). 8-Chloroadenosine 3',5'-monophosphate induces cell cycle arrest and apoptosis in multiple myeloma cells through multiple mechanisms. Oncology Letters, 4, 1384-1388. https://doi.org/10.3892/ol.2012.905
MLA
Cheng, Y., Zhu, Q., Yao, Y., Tang, Y., Wang, M., Zou, L."8-Chloroadenosine 3',5'-monophosphate induces cell cycle arrest and apoptosis in multiple myeloma cells through multiple mechanisms". Oncology Letters 4.6 (2012): 1384-1388.
Chicago
Cheng, Y., Zhu, Q., Yao, Y., Tang, Y., Wang, M., Zou, L."8-Chloroadenosine 3',5'-monophosphate induces cell cycle arrest and apoptosis in multiple myeloma cells through multiple mechanisms". Oncology Letters 4, no. 6 (2012): 1384-1388. https://doi.org/10.3892/ol.2012.905
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