{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T18:16:33Z","timestamp":1759601793089},"reference-count":40,"publisher":"The Endocrine Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Purpose: Protein kinase A (PKA) affects cell proliferation in many cell types and is a potential target for cancer treatment. PKA activity is stimulated by cAMP and cAMP analogs. One such substance, 8-Cl-cAMP, and its metabolite 8-Cl-adenosine (8-Cl-ADO) are known inhibitors of cancer cell proliferation; however, their mechanism of action is controversial. We have investigated the antiproliferative effects of 8-Cl-cAMP and 8-CL-ADO on human thyroid cancer cells and determined PKA\u2019s involvement.<\/jats:p><jats:p>Experimental Design: We employed proliferation and apoptosis assays and PKA activity and cell cycle analysis to understand the effect of 8-Cl-ADO and 8-Cl-cAMP on human thyroid cancer and HeLa cell lines.<\/jats:p><jats:p>Results: 8-Cl-ADO inhibited proliferation of all cells, an effect that lasted for at least 4 d. Proliferation was also inhibited by 8-Cl-cAMP, but this inhibition was reduced by 3-isobutyl-1-methylxanthine; both drugs stimulated apoptosis, and 3-isobutyl-1-methylxanthine drastically reduced 8-Cl-cAMP-induced cell death. 8-Cl-ADO induced cell accumulation in G1\/S or G2\/M cell cycle phases and differentially altered PKA activity and subunit levels. PKA stimulation or inhibition and adenosine receptor agonists or antagonists did not significantly affect proliferation.<\/jats:p><jats:p>Conclusions: 8-Cl-ADO and 8-Cl-cAMP inhibit proliferation, induce cell cycle phase accumulation, and stimulate apoptosis in thyroid cancer cells. The effect of 8-Cl-cAMP is likely due to its metabolite 8-Cl-ADO, and PKA does not appear to have direct involvement in the inhibition of proliferation by 8-Cl-ADO. 8-Cl-ADO may be a useful therapeutic agent to be explored in aggressive thyroid cancer.<\/jats:p>","DOI":"10.1210\/jc.2007-2331","type":"journal-article","created":{"date-parts":[[2007,12,12]],"date-time":"2007-12-12T04:47:23Z","timestamp":1197434843000},"page":"1020-1029","source":"Crossref","is-referenced-by-count":19,"title":["Protein Kinase A-Independent Inhibition of Proliferation and Induction of Apoptosis in Human Thyroid Cancer Cells by 8-Cl-Adenosine"],"prefix":"10.1210","volume":"93","author":[{"given":"Audrey J.","family":"Robinson-White","sequence":"first","affiliation":[{"name":"Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, National Institute of Child Health and Human Development (NICHD) (A.J.R.-W., H.-P.H., E.G., A.B., M.N., C.A.S.), National Institutes of Health (NIH), Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-Pin","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (H.-P.H.), Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Taiwan 812"},{"name":"Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, National Institute of Child Health and Human Development (NICHD) (A.J.R.-W., H.-P.H., E.G., A.B., M.N., C.A.S.), National Institutes of Health (NIH), Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang W.","family":"Leitner","sequence":"additional","affiliation":[{"name":"Dermatology Branch, National Cancer Institute (NCI) (W.W.L.), National Institutes of Health (NIH), Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Greene","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, National Institute of Child Health and Human Development (NICHD) (A.J.R.-W., H.-P.H., E.G., A.B., M.N., C.A.S.), National Institutes of Health (NIH), Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Bauer","sequence":"additional","affiliation":[{"name":"Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics, National Institute of Child Health and Human Development (NICHD) (A.J.R.-W., H.-P.H., E.G., A.B., M.N., C.A.S.), National Institutes of Health (NIH), Bethesda, Maryland 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy L.","family":"Krett","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology (N.L.K.), Department of Medicine, Robert H. 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