DCZ0801, a novel compound, induces cell apoptosis and cell cycle arrest via MAPK pathway in multiple myeloma

2019 ◽  
Vol 51 (5) ◽  
pp. 517-523 ◽  
Author(s):  
Ting Zhang ◽  
Bo Li ◽  
Qilin Feng ◽  
Zhijian Xu ◽  
Cheng Huang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Mapk Pathway ◽  
Cycle Arrest

scholarly journals Rafoxanide, an Organohalogen Drug, Triggers Apoptosis and Cell Cycle Arrest in Multiple Myeloma By Enhancing DNA Damage Responses and Suppressing the p38 MAPK Pathway

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5628-5628
Author(s):  
Jumei Shi ◽  
Wenqin Xiao ◽  
Zhijian Xu ◽  
Shuaikang Chang ◽  
Lu Gao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Cycle Arrest ◽  
P38 Mapk Pathway ◽  
Mouse Xenograft Model ◽  
Synergistic Cytotoxicity

Abstract Rafoxanide is used in veterinary medicine for the treatment of fascioliasis. We previously repositioned the drug as the inhibitor of B-Raf V600E, but its anti-tumor effect in human cancer has never been reported. In this study, we investigated the effects of rafoxanide in multiple myeloma (MM) in vitro and in vivo. We found that rafoxanide inhibited cell proliferation and overcame the protective effect of the bone marrow (BM) microenvironment on MM cells. Rafoxanide induced cell apoptosis by reducing mitochondrial membrane potential (MMP) and regulating the caspase pathway, while having no apparent toxic effect on normal cells. Rafoxanide also inhibited DNA synthesis and caused cell cycle arrest by regulating the cdc25A-degradation pathway. In addition, rafoxanide enhanced the DNA damage response by up-regulating the expression of γ-H2AX. Importantly, as a potent B-Raf V600E inhibitor, rafoxanide could suppress activation of the p38 MAPK pathway. Rafoxanide treatment inhibited tumor growth, with no significant side effects, in an MM mouse xenograft model. Finally, combination of rafoxanide with bortezomib or lenalidomide significantly induced synergistic cytotoxicity in MM cells. Collectively, our results may provide a rationale for use of this drug in MM treatment. This study was supported by grants from the National Natural Science Foundation of China (Nos. 81570190; 81670194 and 81529001). Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Polyphyllin I Induces Cell Cycle Arrest and Cell Apoptosis in Human Retinoblastoma Y-79 Cells through Targeting p53

2018 ◽  
Vol 18 (6) ◽  
pp. 875-881 ◽  
Author(s):  
Xue Zhu ◽  
Ke Wang ◽  
Kai Zhang ◽  
Yi Pan ◽  
Fanfan Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Potential Effect ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
P53 Expression ◽  
Cycle Arrest ◽  
Wide Range ◽  
Human Retinoblastoma

Background: Retinoblastoma is the most common intraocular malignant tumor in childhood. Although external beam radiation and enucleation are effective to control retinoblastoma, eye salvage and vision preservation are still significant challenges. Polyphyllin I (PPI), a natural compound extracted from Paris polyphylla rhizomes, has a wide range of activities against many types of cancers. However, the potential effect of this herbal compound on retinoblastoma has not yet been investigated. Method: In the present study, we evaluated the cytotoxic effect of PPI on human retinoblastoma Y-79 cells as well as its underlying molecular mechanism. Our results indicated that PPI treatment significantly inhibited cell proliferation, arrested the cell cycle at G2/M phase and induced cell apoptosis of Y79 cells through the mitochondrial- dependent intrinsic pathway. Moreover, p53 is involved in PPI-induced cytotoxicity in human retinoblastoma Y-79 cells. Exposure to 10 μM PPI for 48 h dramatically induced the expression levels of p53, phosphorylated- p53 and acetylated-p53. Furthermore, blockade of p53 expression effectively attenuated PPI-induced cell cycle arrest and cell apoptosis in Y-79 cells. Result: These results demonstrated that PPI exhibits anti-proliferation effect on human retinoblastoma Y-79 cells through modulating p53 expression, stabilization and activation. This information shed light on the potential application of PPI in retinoblastoma therapy.

scholarly journals 8-Chloroadenosine 3′,5′-monophosphate induces cell cycle arrest and apoptosis in multiple myeloma cells through multiple mechanisms

2012 ◽  
Vol 4 (6) ◽  
pp. 1384-1388 ◽  
Author(s):  
YI-MIN CHENG ◽  
QI ZHU ◽  
YI-YUN YAO ◽  
YONG TANG ◽  
MING-MING WANG ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Cell Cycle Arrest ◽  
Myeloma Cells ◽  
Cycle Arrest

scholarly journals Propionate of a microbiota metabolite induces cell apoptosis and cell cycle arrest in lung cancer

2019 ◽  
Author(s):  
Kwangkho Kim ◽  
Ohman Kwon ◽  
Tae Ryu ◽  
Cho‑Rok Jung ◽  
Janghwan Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Cycle Arrest
Sign in / Sign up

Export Citation Format

Share Document