Effects of 9-cis-retinoic acid on the proliferation and apoptosis of cutaneous T-cell lymphoma cells

The vitamin A derivative 9-cis-retinoic acid (9-cis-RA) has been used for the treatment and prevention of cutaneous T-cell lymphoma (CTCL). However, the precise mechanism by which 9-cis-RA treatment ameliorates CTCL remains elusive. Our research shows that 9-cis-RA inhibits proliferation and induces apoptosis in CTCL cells in a dose-dependent and time-dependent manner. 9-Cis-RA also induced G0/G1 cell cycle arrest by downregulation of cyclin D1. We confirmed that 9-cis-RA significantly decreased phosphorylation of JAK1, STAT3, and STAT5 and downregulated Bcl-xL and cyclin D1, indicating that 9-cis-RA inhibited the activation of JAK/STAT signaling. Meanwhile, 9-cis-RA also activated classical RA-mediated transcription by retinoic acid receptors (RAR) and/or retinoid X receptors (RXR) in a CTCL cell line. Thus, 9-cis-RA may be effective for chemotherapy and may prevent human CTCL by inhibiting proliferation and inducing apoptosis by inhibition of the JAK/STAT pathway and activation of the RAR/RXR pathway. Correspondence to Pengcheng Ma, PhD, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, 12 Jiangwangmiao Street, Nanjing 210042, China Tel: +86 258 547 8929; fax: +86 258 547 1862; e-mail: mpc815@163.com Received October 28, 2017 Accepted August 6, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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