Antibody Against N-terminal Domain of Phospholipid Scramblase 1 Induces Apoptosis in Colorectal Cancer Cells Through the Intrinsic Apoptotic Pathway

2014 ◽  
Vol 84 (1) ◽  
pp. 36-43 ◽  
Author(s):  
Chun-Yu Chen ◽  
Jinn-Shiun Chen ◽  
Yeh-Pin Chou ◽  
Yung-Bin Kuo ◽  
Chung-Wei Fan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Intrinsic Apoptotic Pathway ◽  
Apoptotic Pathway ◽  
Phospholipid Scramblase ◽  
Terminal Domain ◽  
Colorectal Cancer Cells ◽  
Phospholipid Scramblase 1

SK1 inhibitor RB005 Induces Apoptosis in Colorectal Cancer Cells through SK1 Inhibition Dependent and Independent Pathway

2021 ◽  
Vol 14 ◽  
Author(s):  
Jitendra Shrestha ◽  
Maftuna Shamshiddinova ◽  
Yong-Moon Lee ◽  
Yoon-Sin Oh ◽  
Dong Jae Baek ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Apoptotic Cell ◽  
Colon Cancer Cell ◽  
Lipid Mediator ◽  
Intrinsic Apoptotic Pathway ◽  
Apoptotic Pathway

Background and Objective: Colorectal cancer (CRC) is the fourth leading cause of cancer-related death globally, with a high incidence rate in economically fast-growing countries. Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that plays critical roles in cancer cell proliferation, migration, and angiogenesis converted by the isoforms of sphingosine kinase (SK1 and SK2). SK1 is highly expressed in colorectal cancer, its inhibitors suppress the formation of S1P and increase ceramide levels having a pro-apoptotic function. RB005 is a selective SK1 inhibitor and a structural analog of PP2A activator FTY720. The purpose of this study is to test whether RB005, an SK1 inhibitor, can be used as an anticancer agent by inhibiting the growth of colon cancer cells. Methods: We performed MTT and colony-forming assay using colon cancer cell lines HT29 and HCT116 cells to examine the cell toxicity effect of RB005. To determine whether apoptosis of RB005 in colon cancer cell line is due to SK1 inhibition or other mechanisms due to its structural similarity with FTY720, we conducted LC/MS, siRNA knockdown, and PP2A activity experiments. Results: RB005 notably inhibited CRC cell growth and proliferation compared to PF543 and ABC294640 by inducing the mitochondria-mediated intrinsic apoptotic pathway. Apoptotic cell death is caused by increased mitochondrial permeability necessitated by the activation of pro-apoptotic protein BAX, increased ceramides, and activation of PP2A. Also, RB005 treatment in HT29 cells did not change the expression level of SK1, but strikingly decreased SK1 activity and S1P levels. All these events of cell death and apoptosis were less effective when SK1 was knocked down by siRNA. Conclusion: This result indicates that RB005 shows the in-vitro anti-CRC effect by inhibiting SK1 activity and PP2A activation, increasing proapoptotic ceramide levels following the activation of the intrinsic apoptotic pathway.

Theragnosis by a miR-141-3p molecular beacon: simultaneous detection and sensitization of 5-fluorouracil resistant colorectal cancer cells through the activation of the TRIM13-associated apoptotic pathway

2019 ◽  
Vol 55 (52) ◽  
pp. 7466-7469 ◽  
Author(s):  
Sung Ung Moon ◽  
Yongkeun Park ◽  
Min Geun Park ◽  
Sung Kyu Song ◽  
Seok Hoo Jeong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Molecular Beacon ◽  
Simultaneous Detection ◽  
Apoptotic Pathway ◽  
Colorectal Cancer Cells ◽  
Therapy And Diagnosis

Schematic of the ‘therapy and diagnosis at once (theragnosis)’ for 5-FU resistant colorectal cancer using the miR-141-3p molecular beacon.

scholarly journals Synergistic Suppression Effect on Tumor Growth of Colorectal Cancer by Combining Radiotherapy With a TRAIL-Armed Oncolytic Adenovirus

2019 ◽  
Vol 18 ◽  
pp. 153303381985329 ◽  
Author(s):  
Hangxiang Gao ◽  
Xin Zhang ◽  
Ying Ding ◽  
Rong Qiu ◽  
Yupeng Hong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Necrosis Factor ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Tumor Necrosis ◽  
Xenograft Model ◽  
Oncolytic Adenovirus ◽  
Apoptotic Pathway ◽  
Colorectal Cancer Cells ◽  
Necrosis Factor

The combination of gene therapy and radiation is a promising new treatment for cancer. This study aimed to clarify the synergistic effect of targeted oncolytic adenovirus (radiotherapy-tumor necrosis factor-related apoptosis-inducing ligand) and radiotherapy on colorectal cancer cells and elucidate the mechanisms of the underlying antitumor activity. Viability, cell cycle status, and apoptosis of treated colorectal cancer cells were determined via MTT and flow cytometric assays. The molecular mechanism underlying apoptotic pathway activation was elucidated through Western blot analysis of caspase-8, caspase-3, and PARP proteins. Combination treatment with radiotherapy-tumor necrosis factor-related apoptosis-inducing ligand and radiotherapy displayed significantly greater antitumor activity than either of the monotherapies. The primary mechanism behind the antitumor activity in the SW480 and Lovo colorectal cancer cell lines was apoptosis induction through the caspase pathway and G1 phase arrest. In an SW480 xenograft model of colorectal cancer, the combination therapy achieved a significantly greater reduction in tumor volume than the monotherapies. Overall, in this study, we demonstrate that the oncolytic radiotherapy-tumor necrosis factor-related apoptosis-inducing ligand construct can sensitize human colorectal cancer cells to radiation-induced apoptosis both in vitro and in vivo. Therefore, our findings point toward a novel synergistic approach to colorectal cancer treatment.

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