Inhibition of 6-Methylsulfinylhexyl Isothiocyanate for Cell Cycle Progression in Quiescent JB6 Cells Stimulated with Fetal Bovine Serum, Accompanied by Suppression of Cyclin A2 Expression

2021 ◽  
pp. 43-59
Author(s):  
Takashi Hashimoto ◽  
Maki Kobayashi ◽  
Kazuki Kanazawa
2021 ◽  
Vol 22 (19) ◽  
pp. 10777
Author(s):  
Donghee Kim ◽  
Hyo-Jin Kim ◽  
Jin-Ok Baek ◽  
Joo-Young Roh ◽  
Hee-Sook Jun

Psoriasis is a chronic inflammatory skin disease. Recently, lysophosphatidic acid (LPA)/LPAR5 signaling has been reported to be involved in both NLRP3 inflammasome activation in macrophages and keratinocyte activation to produce inflammatory cytokines, contributing to psoriasis pathogenesis. However, the effect and molecular mechanisms of LPA/LPAR signaling in keratinocyte proliferation in psoriasis remain unclear. In this study, we investigated the effects of LPAR1/3 inhibition on imiquimod (IMQ)-induced psoriasis-like mice. Treatment with the LPAR1/3 antagonist, ki16425, alleviated skin symptoms in IMQ-induced psoriasis-like mouse models and decreased keratinocyte proliferation in the lesion. It also decreased LPA-induced cell proliferation and cell cycle progression via increased cyclin A2, cyclin D1, cyclin-dependent kinase (CDK)2, and CDK4 expression and decreased p27Kip1 expression in HaCaT cells. LPAR1 knockdown in HaCaT cells reduced LPA-induced proliferation, suppressed cyclin A2 and CDK2 expression, and restored p27Kip1 expression. LPA increased Rho-associated protein kinase 2 (ROCK2) expression and PI3K/AKT activation; moreover, the pharmacological inhibition of ROCK2 and PI3K/AKT signaling suppressed LPA-induced cell cycle progression. In conclusion, we demonstrated that LPAR1/3 antagonist alleviates IMQ-induced psoriasis-like symptoms in mice, and in particular, LPAR1 signaling is involved in cell cycle progression via ROCK2/PI3K/AKT pathways in keratinocytes.


2009 ◽  
Author(s):  
Jianzhi Pan ◽  
Koji Nakade ◽  
Satoko Masuzaki ◽  
Hitomi Hasegawa ◽  
Yu-Chang Huang ◽  
...  

Author(s):  
Takashi Hashimoto ◽  
Maki Kobayashi ◽  
Kazuki Kanazawa

Objective: The effects of 6-MSITC on cell cycle progression were investigated in quiescent mouse epidermal JB6 cells. Background: 6-Methylsulfinylhexyl isothiocyanate (6-MSITC) derived from wasabi (Wasabia japonica) has been reported to prevent tumor development in vivo. Material and methods: Treatment with epidermal growth factor (EGF) to quiescent JB6 cells, which were serum-starved for 36 h, promoted cell cycle progression from the G0/G1 phase to the S phase. Effects of pretreatment with 6-MSITC on cell cycle progression were estimated by flowcytometry and real-time RT-PCR. Results: Pretreatment with 6-MSITC at 0.25-1.0 μg/ml prior to the growth stimulation with EGF significantly inhibited cell cycle progression. Pretreatment with 6-MSITC inhibited the gene expression of DNA synthesis-related proteins cyclin A2, dumbbell former 4, and proliferating cell nuclear antigen. Conclusion: These results showed that 6-MSITC inhibits cell cycle progression in quiescent cells, accompanied by the inhibition of gene expression of DNA synthesis proteins.


Oncogene ◽  
2011 ◽  
Vol 30 (33) ◽  
pp. 3648-3648
Author(s):  
J Pan ◽  
K Nakade ◽  
Y-C Huang ◽  
Z-W Zhu ◽  
S Masuzaki ◽  
...  

2012 ◽  
Vol 3 (6) ◽  
pp. 535-543 ◽  
Author(s):  
Nawal Bendris ◽  
Abdelhalim Loukil ◽  
Caroline Cheung ◽  
Nikola Arsic ◽  
Cosette Rebouissou ◽  
...  

AbstractCyclin A2 belongs to the core cell cycle regulators and participates in the control of both S phase and mitosis. However, several observations suggest that it is also endowed with other functions, and our recent data shed light on its involvement in cytoskeleton dynamic and cell motility. From the transcription of its gene to its posttranslational modifications, cyclin A2 regulation reveals the complexity of the regulatory network shaping cell cycle progression. We summarize our current knowledge on this cell cycle regulator and discuss recent findings raising the possibility that cyclin A2 might play a much broader role in epithelial tissues homeostasis.


2021 ◽  
Vol Volume 14 ◽  
pp. 3443-3454
Author(s):  
Haoran Wang ◽  
Zixiang Liu ◽  
Peng Wu ◽  
Hanqing Wang ◽  
Weiwei Ren

Oncogene ◽  
2010 ◽  
Vol 29 (47) ◽  
pp. 6245-6256 ◽  
Author(s):  
J Pan ◽  
K Nakade ◽  
Y-C Huang ◽  
Z-W Zhu ◽  
S Masuzaki ◽  
...  

2015 ◽  
Vol 35 (20) ◽  
pp. 3547-3565 ◽  
Author(s):  
Yixuan Li ◽  
Lirong Peng ◽  
Edward Seto

Histone deacetylase (HDAC) inhibition leads to cell cycle arrest in G1and G2, suggesting HDACs as therapeutic targets for cancer and diseases linked to abnormal cell growth and proliferation. Many HDACs are transcriptional repressors. Some may alter cell cycle progression by deacetylating histones and repressing transcription of key cell cycle regulatory genes. Here, we report that HDAC10 regulates the cell cycle via modulation of cyclin A2 expression, and cyclin A2 overexpression rescues HDAC10 knockdown-induced G2/M transition arrest. HDAC10 regulates cyclin A2 expression by deacetylating histones near thelet-7promoter, thereby repressing transcription. InHDAC10knockdown cells,let-7fand microRNA 98 (miR-98) were upregulated and thelet-7family target,HMGA2, was downregulated. HMGA2 loss resulted in enrichment of the transcriptional repressor E4F at the cyclin A2 promoter. These findings support a role for HDACs in cell cycle regulation, reveal a novel mechanism of HDAC10 action, and extend the potential of HDACs as targets in diseases of cell cycle dysregulation.


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