Reactive Oxygen Species and p53 Mediated Activation of p38 and Caspases is Critically Involved in Kaempferol Induced Apoptosis in Colorectal Cancer Cells

2018 ◽  
Vol 66 (38) ◽  
pp. 9960-9967 ◽  
Author(s):  
Jhin-Baek Choi ◽  
Ju-Ha Kim ◽  
Hyemin Lee ◽  
Ji-Na Pak ◽  
Bum Sang Shim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Colorectal Cancer Cells ◽  
Induced Apoptosis

scholarly journals Hellebrigenin induces apoptosis in colorectal cancer Cells through induction of excessive reactive oxygen species

BIOCELL ◽  
2021 ◽  
Vol 45 (4) ◽  
pp. 943-951
Author(s):  
CHUNJIAO LIU ◽  
QINHONG KONG ◽  
FENG PAN ◽  
SHAN JIANG ◽  
LINGJIE MENG ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Colorectal Cancer Cells

scholarly journals A novel coordination complex of platinum (PT) induces cell death in colorectal cancer by altering redox balance and modulating MAPK pathway

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Khayal Al-Khayal ◽  
Mansoor-Ali Vaali-Mohammed ◽  
Mohammed Elwatidy ◽  
Thamer Bin Traiki ◽  
Omar Al-Obeed ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Mitochondrial Membrane ◽  
Mapk Pathway ◽  
Platinum Complex ◽  
Oxygen Species ◽  
Cytochrome C Release ◽  
Colorectal Cancer Cells ◽  
Induced Apoptosis

Abstract Background Colorectal cancer (CRC) is a heterogeneous tumor having various genetic alterations. The current treatment options had limited impact on disease free survival due to therapeutic resistance. Novel anticancer agents are needed to treat CRC specifically metastatic colorectal cancer. A novel coordination complex of platinum, (salicylaldiminato)Pt(II) complex with dimethylpropylene linkage (PT) exhibited potential anti-cancer activity. In this study, we explored the molecular mechanism of PT-induced cell death in colorectal cancer. Methods Colony formation was evaluated using the clonogenic assay. Apoptosis, cell cycle analysis, reactive oxygen species, mitochondrial membrane potential and caspase-3/− 7 were assessed by flow cytometry. Glutathione level was detected by colorimetric assay. PT-induced alteration in pro-apoptotic/ anti-apoptotic proteins and other signaling pathways were investigated using western blotting. P38 downregulation was performed using siRNA. Results In the present study, we explored the molecular mechanism of PT-mediated inhibition of cell proliferation in colorectal cancer cells. PT significantly inhibited the colony formation in human colorectal cancer cell lines (HT-29, SW480 and SW620) by inducing apoptosis and necrosis. This platinum complex was shown to significantly increase the reactive oxygen species (ROS) generation, depletion of glutathione and reduced mitochondrial membrane potential in colorectal cancer cells. Exposure to PT resulted in the downregulation of anti-apoptotic proteins (Bcl2, BclxL, XIAP) and alteration in Cyclins expression. Furthermore, PT increased cytochrome c release into cytosol and enhanced PARP cleavage leading to activation of intrinsic apoptotic pathway. Moreover, pre-treatment with ROS scavenger N-acetylcysteine (NAC) attenuated apoptosis suggesting that PT-induced apoptosis was driven by oxidative stress. Additionally, we show that PT-induced apoptosis was mediated by activating p38 MAPK and inhibiting AKT pathways. This was demonstrated by using chemical inhibitor and siRNA against p38 kinase which blocked the cytochrome c release and apoptosis in colorectal cancer cells. Conclusion Collectively, our data demonstrates that the platinum complex (PT) exerts its anti-proliferative effect on CRC by ROS-mediated apoptosis and activating p38 MAPK pathway. Thus, our findings reveal a novel mechanism of action for PT on colorectal cancer cells and may have therapeutic implication.

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