Isoliquiritigenin induces apoptosis through caspases and reactive oxygen species signaling pathways in human bladder cancer cells

2020 ◽  
Vol 16 (71) ◽  
pp. 574
Author(s):  
ByungJoo Kim ◽  
Minwoo Hwang ◽  
MinJi Kwon
Keyword(s):  
Reactive Oxygen Species ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Oxygen Species ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Bladder Cancer Cells ◽  
Reactive Oxygen Species Signaling ◽  
Human Bladder Cancer Cells

scholarly journals Isorhamnetin Induces Cell Cycle Arrest and Apoptosis Via Reactive Oxygen Species-Mediated AMP-Activated Protein Kinase Signaling Pathway Activation in Human Bladder Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1494 ◽  
Author(s):  
Park ◽  
Cha ◽  
Choi ◽  
Lee ◽  
Hwang-Bo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Oxygen Species ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Anti Cancer ◽  
Bladder Cancer Cells ◽  
M Phase ◽  
Human Bladder Cancer Cells

Isorhamnetin is an O-methylated flavonol that is predominantly found in the fruits and leaves of various plants, which have been used for traditional herbal remedies. Although several previous studies have reported that this flavonol has diverse health-promoting effects, evidence is still lacking for the underlying molecular mechanism of its anti-cancer efficacy. In this study, we examined the anti-proliferative effect of isorhamnetin on human bladder cancer cells and found that isorhamnetin triggered the gap 2/ mitosis (G2/M) phase cell arrest and apoptosis. Our data showed that isorhamnetin decreased the expression of Wee1 and cyclin B1, but increased the expression of cyclin-dependent kinase (Cdk) inhibitor p21WAF1/CIP1, and increased p21 was bound to Cdk1. In addition, isorhamnetin-induced apoptosis was associated with the increased expression of the Fas/Fas ligand, reduced ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein (Bax) expression, cytosolic release of cytochrome c, and activation of caspases. Moreover, isorhamnetin inactivated the adenosine 5′-monophosphate-activated protein kinase (AMPK) signaling pathway by diminishing the adenosine triphosphate (ATP) production due to impaired mitochondrial function. Furthermore, isorhamnetin stimulated production of intracellular reactive oxygen species (ROS); however, the interruption of ROS generation using a ROS scavenger led to an escape from isorhamnetin-mediated G2/M arrest and apoptosis. Collectively, this is the first report to show that isorhamnetin inhibited the proliferation of human bladder cancer cells by ROS-dependent arrest of the cell cycle at the G2/M phase and induction of apoptosis. Therefore, our results provide an important basis for the interpretation of the anti-cancer mechanism of isorhamnetin in bladder cancer cells and support the rationale for the need to evaluate more precise molecular mechanisms and in vivo anti-cancer properties.

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