title: The molecular mechanism of curcumol on inducing cell growth arrest and apoptosis in Jurkat cells, a model of CD4⁺ T cells.
abstract: CD4(+) T cells in rheumatoid arthritis (RA) express growth signaling pathway in association with deregulated growth and resistance to apoptosis. The janus kinase (Jak) 3 and signal transducer and activator of transcription (STAT) pathway play a critical role in interleukin-2 (IL-2)-induced CD4(+) T cell proliferation. The present study aimed to explore the anti-cell proliferation mechanism of curcumol, a pure monomer extracted from Chinese medical plant Rhizoma curcumae. Cell proliferation was determined using WST-1 assay after curcumol treatment. The cell cycle distribution and Bcl-2 protein expression were assessed by flow cytometry. The cellular morphology of apoptosis was evaluated by Hoechst 33258 staining. The expressions of phosphorylated-Jak3 (p-Jak3), p-STAT3, and p-STAT5a following IL-2 stimulation were determined by western blot analysis. The Electrophoretic Mobility Shift Assay was used to detect the DNA binding activities of transcription factors STAT3 and STAT5. The study results showed that curcumol could inhibit the IL-2-induced Jurkat cell proliferation in a concentration- and time-dependent manner in vitro. Curcumol could cause cell cycle arrest at the S phase, induce cell apoptosis, and inhibit the expression of Bcl-2 in a dose-dependent manner. Curcumol at 50μg/mL and Jak3 inhibitor ZM39923 could inhibit the phosphorylation of Jak3 and STAT5a. In conclusion, the underlying mechanism of curcumol on suppressing CD4(+) T cell proliferation and inducing apoptosis might partly be mediated by inhibition of Jak3-STAT5-related molecular activities and Bcl-2 expression, respectively; further studies are required in vivo to test the use of curcumol as a promising therapeutic option for RA.
authors.affiliation: Department of Traditional Chinese Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China; Department of Rheumatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China. Electronic address: wangyongjhy@126.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Xiaoji
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Traditional Chinese Medicine, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Rheumatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhong
authors.affiliation: Department of Rheumatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China. Electronic address: fangyongfei@qq.com.
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Fang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D053616:Janus Kinase 3 / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D004365:Drugs, Chinese Herbal; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D012717:Sesquiterpenes; D025521:Tumor Suppressor Proteins; C022801:curcumol; C507933:JAK3 protein, human; D053616:Janus Kinase 3
keywords: Curcumol; Jak3–STAT; Jurkat cells; Mechanism; Rheumatoid arthritis