Cigarette tar phenols impede T cell cycle progression by inhibiting cyclin-dependent kinases.
Cigarette smoking causes profound suppression of pulmonary T cell responses, which is associated with increased susceptibility to respiratory tract infections and decreased tumor surveillance. We previously demonstrated that the phenolic compounds in cigarette tar inhibit blastogenesis and interfere with human T cell cycle progression. To identify the mechanism by which cell cycle arrest occurs, we examined the effects of these compounds on cyclin-dependent kinases (Cdk) that control the G0/G1 transition. We found that hydroquinone inhibited induction of Cdk4 and Cdk6 kinase activities by >80%, while catechol and phenol were markedly less potent. HQ did not affect mitogenic induction of the Cdk6 protein, but inhibited expression of cyclin D3 by >90% resulting in a dramatic reduction in proper Cdk6/Cyclin D3 complex formation.
Division of Allergy and Clinical Immunology, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA.
Ashley A
AA
Frazer-Abel
Jesica M
JM
McCue
Sabine
S
Lazis
Mary
M
Portas
Cherie
C
Lambert
Brian M
BM
Freed
D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors* / Q000276:immunology; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors* / Q000276:immunology; D004790:Enzyme Induction / Q000187:drug effects; D016193:G1 Phase; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D010636:Phenols / Q000633:toxicity; D016192:Resting Phase, Cell Cycle; D012907:Smoking / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D013638:Tars / Q000633:toxicity*
D010636:Phenols; D013638:Tars; C024746:tobacco tar; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6