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

Abstract

Abstract. The aim of this study was to investigate the molecular mechanism of 8-chloroadenosine 3',5 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 proapoptotic 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.

Visualization and bibliometric analysis of cAMP signaling system research trends and hotspots in cancer

“…Daniel PM et al proposed that the pharmacological activation of cAMP in glioblastoma (GBM) cells led to the increase of proapoptotic BIM (Bcl-2 interacting mediator of cell death) expression and apoptosis in specific types of GBM cells 17 . Cheng YM et al and Follin-Arbelet V et al showed that cAMP could induce apoptosis in multiple myeloma cells in vitro 43 , 44 . However, Hara M et al showed that vasoactive intestinal peptide could prevent the progression of hepatocellular carcinoma (HCC) by increasing apoptosis through inhibiting cAMP / Bcl-xL pathway 45 .…”

“…According to the above results, several frontiers and hotspots of research focus on cAMP signaling system in cancer field were extracted as follows: cAMP signaling pathway is related to cancer cell apoptosis Generally, cAMP signaling pathway was confirmed to be inhibited in many reported cancer tissues [17]. A lot of studies have shown that if the cAMP level in cancer tissue is enhanced, the apoptosis of tumor cells can be promoted, thus inhibiting tumor growth [42,43,44]. Abudoureyimu A et al found that As2O3 induced gastric cancer BGC-823 cell apoptosis by up regulating cAMP level and down regulating PKC level [42].…”