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

Yang, Huaa; Tao, Yueb; Zhang, Menglic; Ma, Pengchengc; Li, Lingjunc; Diao, Qingchuna

doi: 10.1097/CAD.0000000000000692
PRECLINICAL REPORTS
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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.

aDepartment of Dermatology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing

bDepartment of Dermatology, Drum Tower Hospital, Medical School of Nanjing University

cInstitute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Nanjing, China

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

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