scholarly journals All-Trans Retinoic Acid Induces DU145 Cell Cycle Arrest through Cdk5 Activation

2014 ◽  
Vol 33 (6) ◽  
pp. 1620-1630 ◽  
Author(s):  
Eugene Lin ◽  
Mei-Chih Chen ◽  
Chih-Yang Huang ◽  
Shih-Lan Hsu ◽  
William J. Huang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Retinoic Acid ◽  
Cell Cycle Arrest ◽  
Du145 Cell ◽  
Cycle Arrest ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals In Vitro Anticancer Effects of All-trans Retinoic Acid in Combination with Dacarbazine against CD117+ Melanoma Cells

Drug Research ◽  
2020 ◽  
Vol 70 (12) ◽  
pp. 563-569
Author(s):  
Bahareh Mohammadi Jobani ◽  
Elham Mohebi ◽  
Nowruz Najafzadeh
Keyword(s):  
Cell Cycle ◽  
Retinoic Acid ◽  
Malignant Melanoma ◽  
Cell Cycle Arrest ◽  
Combined Treatment ◽  
Melanoma Cells ◽  
Cycle Arrest ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Background Malignant melanoma is a common form of skin cancer that contains different cell types recognized by various cell surface markers. Dacarbazine-based combination chemotherapy is frequently used for the treatment of melanoma. Despite its potent anticancer properties, resistance to dacarbazine develops in malignant melanoma. Here, we aim to improve response to dacarbazine therapy by pretreatment with all-trans retinoic acid (ATRA) in CD117+ melanoma cells. Methods The CD117+ melanoma cells were sorted from A375 malignant melanoma cell line using magnetic-activated cell sorting (MACS). The cell viability was examined by cell proliferation assay (MTT). Apoptosis was determined by acridine orange/ ethidium bromide staining. Indeed, we performed flow cytometry to evaluate the cell cycle arrest. Results Here, the CD117+ melanoma cells were incubated with various concentrations of ATRA, dacarbazine, and their combination to determine IC50 values. We found that 20 µM ATRA treatment followed by dacarbazine was found to be more effective than dacarbazine alone. There was an indication that the combination of ATRA with dacarbazine (ATRA/dacarbazine) caused more apoptosis and necrosis in the melanoma cells (P<0.05). Furthermore, ATRA/dacarbazine treatment inhibited the cell at the G0/G1 phase, while dacarbazine alone inhibited the cells at S phase. Conclusion Collectively, combined treatment with ATRA and dacarbazine induced more apoptosis and enhanced the cell cycle arrest of CD117+ melanoma cells. These results suggested that ATRA increased the sensitivity of melanoma cells to the effect of dacarbazine.

scholarly journals RNAi screen identifies UBE2D3 as a mediator of all-trans retinoic acid-induced cell growth arrest in human acute promyelocytic NB4 cells

Blood ◽  
2007 ◽  
Vol 110 (2) ◽  
pp. 640-650 ◽  
Author(s):  
Hidenori Hattori ◽  
Xueqing Zhang ◽  
Yonghui Jia ◽  
Kulandayan K. Subramanian ◽  
Hakryul Jo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Retinoic Acid ◽  
Cell Growth ◽  
Cyclin D1 ◽  
Cell Cycle Arrest ◽  
Growth Arrest ◽  
Cycle Arrest ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract All-trans retinoic acid (ATRA) has been widely used in differentiation therapy for acute promyelocytic leukemia (APL). ATRA binds to retinoic acid receptor (RAR) and triggers the formation of the transcription coactivator complex, which leads to changes in gene expression, APL cell-cycle arrest and differentiation, and clinical remission. The mechanisms responsible for ATRA's beneficial effects are still ill-defined. Here, we conducted a large-scale, unbiased short hairpin RNA (shRNA) screen aiming to identify mediators of ATRA-induced differentiation and growth arrest of APL cells. Twenty-six proteins were identified. They cover a wide range of cellular functions, including gene expression, intracellular signaling, cell death control, stress responses, and metabolic regulation, indicating the complexity of ATRA-induced cell growth control and differentiation in APL. One of these proteins, the ubiquitin-conjugating enzyme UBE2D3, is up-regulated in ATRA-treated acute promyelocytic NB4 cells. UBE2D3 is physically associated with cyclin D1 and mediates ATRA-induced cyclin D1 degradation. Knocking down UBE2D3 by RNA interference (RNAi) leads to blockage of ATRA-induced cyclin D1 degradation and cell-cycle arrest. Thus, our results highlight the involvement of the ubiquitin-mediated proteolysis pathway in ATRA-induced cell-cycle arrest and provide a novel strategy for modulating ATRA-elicited cellular effects.

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