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- Title
All- trans retinoic acid induces cell-cycle arrest in human cutaneous squamous carcinoma cells by inhibiting the mitogen-activated protein kinase-activated protein 1 pathway.
- Authors
Zhang, M.‐l.; Tao, Y.; Zhou, W.‐q.; Ma, P.‐c.; Cao, Y.‐p.; He, C.‐d.; Wei, J.; Li, L.‐j.
- Abstract
Background All- trans retinoic acid (ATRA) has been tried for the treatment and prevention of a number of epithelial cancers. However, the precise mechanism by which ATRA inhibits the growth of cutaneous squamous cell carcinoma ( cSCC) remains elusive. Aims To determine the suppressive effects of ATRA on the human cSCC cell line SCL-1, and explore the possible mechanisms involved. Methods SCL-1 cells were treated with ATRA, then cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide ( MTT) assay, while apoptosis and cell cycle progression were analysed by flow cytometry. Protein levels of cell-cycle regulatory proteins and the activation of extracellular signal-regulated kinase ( ERK) and Jun kinase ( JNK) were detected by western blotting analysis. Transcriptional activity of activator protein ( AP)-1 was examined by luciferase reporter assay. Results ATRA inhibited the proliferation of SCL-1 cells and had modest proapoptotic effects. ATRA also induced G1 cell-cycle arrest, inhibited the expression of cyclin D1/cyclin-dependent kinase ( CDK)4 and cyclinE/ CDK2, and increased the expression of the cyclin-dependent kinase inhibitors p21 and p27. In addition, ATRA significantly decreased the phosphorylation of ERK1/2 and JNK1/2, and inhibited AP-1 transcriptional activity. Conclusions ATRA induces cell-cycle arrest in human cSCC cells by inhibiting the mitogen-activated protein kinase (MAPK)-AP1 pathway, and could be effective in the prevention and chemotherapy of human cSCC.
- Subjects
TRETINOIN; SQUAMOUS cell carcinoma; CELLULAR mechanics; CELL cycle; CYCLIN-dependent kinase inhibitors; CANCER chemotherapy
- Publication
Clinical & Experimental Dermatology, 2014, Vol 39, Issue 3, p354
- ISSN
0307-6938
- Publication type
Article
- DOI
10.1111/ced.12227