Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-6-6
pubmed:abstractText
8-Cl-cyclic adenosine monophosphate (8-Cl-cAMP) has been known to induce growth inhibition and differentiation in a variety of cancer cells by differential modulation of protein kinase A isozymes. To understand the anticancer activity of 8-Cl-cAMP further, we investigated the effect of 8-Cl-cAMP on apoptosis in human cancer cells. Most of the tested human cancer cells exhibited apoptosis upon treatment with 8-Cl-cAMP, albeit with different sensitivity. Among them, SH-SY5Y neuroblastoma cells and HL60 leukemic cells showed the most extensive apoptosis. The effect of 8-Cl-cAMP was not reproduced by other cAMP analogues or cAMP-elevating agents, showing that the effect of 8-Cl-cAMP was not caused by simple activation of protein kinase A (PKA). However, competition experiments showed that the binding of 8-Cl-cAMP to the cAMP receptor was essential for the induction of apoptosis. After the treatment of 8-Cl-cAMP, cells initially accumulated at the S and G2/M phases of the cell cycle and then apoptosis began to occur among the population of cells at the S/G2/M cell cycle phases, indicating that the 8-Cl-cAMP-induced apoptosis is closely related to cell cycle control. In support of this assumption, 8-Cl-cAMP-induced apoptosis was blocked by concomitant treatment with mimosine, which blocks the cell cycle at early S phase. Interestingly, 8-Cl-cAMP did not induce apoptosis in primary cultured normal cells and non-transformed cell lines, showing that 8-Cl-cAMP-induced apoptosis is specific to transformed cells. Taken together, our results show that the induction of apoptosis is one of the mechanisms through which 8-Cl-cAMP exerts anticancer activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33-41
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11391618-3T3 Cells, pubmed-meshheading:11391618-8-Bromo Cyclic Adenosine Monophosphate, pubmed-meshheading:11391618-Animals, pubmed-meshheading:11391618-Antineoplastic Agents, pubmed-meshheading:11391618-Apoptosis, pubmed-meshheading:11391618-Breast Neoplasms, pubmed-meshheading:11391618-CHO Cells, pubmed-meshheading:11391618-Cell Cycle, pubmed-meshheading:11391618-Cricetinae, pubmed-meshheading:11391618-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:11391618-Female, pubmed-meshheading:11391618-G2 Phase, pubmed-meshheading:11391618-HL-60 Cells, pubmed-meshheading:11391618-HeLa Cells, pubmed-meshheading:11391618-Humans, pubmed-meshheading:11391618-K562 Cells, pubmed-meshheading:11391618-Mice, pubmed-meshheading:11391618-Mitosis, pubmed-meshheading:11391618-Neuroblastoma, pubmed-meshheading:11391618-Ovarian Neoplasms, pubmed-meshheading:11391618-Receptors, Cyclic AMP, pubmed-meshheading:11391618-S Phase, pubmed-meshheading:11391618-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
8-Cl-cAMP induces cell cycle-specific apoptosis in human cancer cells.
pubmed:affiliation
School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't