scholarly journals Intracellular expression of arginine deiminase activates the mitochondrial apoptosis pathway through inhibiting cytosolic ferritin and inducing chromotin autophagy

2020 ◽  
Author(s):  
Qingyuan Feng ◽  
Xuzhao Bian ◽  
Xuan Liu ◽  
Ying Wang ◽  
Huiting Zhou ◽  
...  
Keyword(s):  
Cell Death ◽  
Western Blot ◽  
Cancer Cell ◽  
Malignant Tumors ◽  
Mitochondrial Damage ◽  
Arginine Deiminase ◽  
Immunofluorescent Staining ◽  
Apoptosis Pathway ◽  
P53 Expression ◽  
Cancer Cell Death

Abstract Background：Based on its low toxicity, arginine starvation therapy has the potential to treat those malignant tumors that can’t be treated by surgery. Arginine deiminase (ADI) gene is indicated to be an ideal cancer-suppressor gene. ADI expressed in cytosol displays higher oncolytic efficiency than ADI-PEG20 (Pegylated Arginine Deiminase by PEG 20,000). However, it is still unknown whether cytosolic ADI has the same function mechanism as ADI-PEG20 or other underlying mechanisms in cells.Methods: The interaction of ADI and other protein factors was screened by yeast hybrid, and verified by co-immunoprecipitation and immunofluorescent staining. The effect of ADI inhibiting ferritin light-chain domain (FTL) on mitochondrial damage was evaluated by site-directed mutation and flow cytometry. The apoptosis pathway of mitochondria control was analyzed by Western Blot and real-time PCR experiments. The effect of p53 expression on cancer cell death was assessed by siTP53 transfection. The chromatin autophagy was explored by immunofluorescent staining and Western Blot.Results: ADI expressed in cytosol inhibited the activity of cytosolic ferritin through interacting with FTL. The inactive mutant of ADI still induced the apoptosis in certain cell lines of ASS- through mitochondrial damage. Arginine starvation also induced the increased expression of p53 and p53AIP1, which aggravate cellular mitochondrial damage. Chromatin autophagy appeared at the later stage of arginine starvation. DNA damage came along with the whole process of arginine starvation. Histone 3 (H3) was found in autophagosomes, which implied that cancer cells try to utilize the arginine in histones to survive during arginine starvation. Conclusions: Mitochondrial damage is the major mechanism of cell death induced by cytosolic ADI. Chromatophagy accumulations not only drive cancer cell to utilize histone arginine but also speed up cancer cell death at the later time point of arginine starvation.

scholarly journals Arginine deimimase expressed in vivo activates the mitochondrial apoptosis pathway through inhibiting cytosolic ferritin and inducing chromotin autophagy

2020 ◽  
Author(s):  
Qingyuan Feng ◽  
Xuzhao Bian ◽  
Xuan Liu ◽  
Ying Wang ◽  
Huiting Zhou ◽  
...  
Keyword(s):  
Cell Death ◽  
Western Blot ◽  
Cancer Cell ◽  
Malignant Tumors ◽  
Arginine Deiminase ◽  
Immunofluorescent Staining ◽  
Apoptosis Pathway ◽  
P53 Expression ◽  
Cancer Cell Death

Abstract BackgroundBased on its low toxicity, arginine starvation therapy has the potential to treat those malignant tumors that can’t be treated by surgery. Arginine deiminase (ADI) gene is indicated to be an idea cancer-suppressor gene. ADI expressed in vivo displays higher oncolytic efficiency than ADI-PEG20 (Pegylated Arginine Deiminase by PEG 20,000)[1]. However, it is still unknown whether cytosolic ADI has the same function mechanism as ADI-PEG20 or other underlying mechanisms in cells.MethodsThe interaction of ADI and other protein factors was screened by yeast hybrid, and verified by co-immunoprecipitation and immunofluorescent staining. The effect of ADI inhibiting ferritin light-chain domain (FTL) on mitochondria damage was evaluated by site-directed mutation and flow cytometry. The apoptosis pathway of mitochondria control was analyzed by Western Blot and real-time PCR. The effect of p53 expression on cancer cell death was assessed by siTP53 transfection. The chromatin autophagy was explored by immunofluorescent staining and Western Blot.ResultsADI expressed in vivo inhibited the activity of cytosolic ferritin through interacting with FTL. The inactive mutant of ADI still aroused the apoptosis of some cells through mitochondria damage. Arginine starvation also induced the expression increase of p53 and p53AIP1, which aggravate cellular mitochondria damage. Chromatin autophagy appeared at the later stage of arginine starvation. DNA damage came along with the whole process of arginine starvation. Histone 3 (H3) was found in autophagosomes, which implied that cancer cells try to utilize the arginine in histones to survive during arginine starvation.Conclusions: Mitochondria damage is the major mechanism for ADI expressed in vivo to induce cancer cell death. Chromatophagy accumulations not only drive cancer cell to utilize histone arginine but also speed up cancer cell death at the later time point of arginine starvation.

scholarly journals Intracellular expression of arginine deimimase activates the mitochondrial apoptosis pathway through inhibiting cytosolic ferritin and inducing chromotin autophagy

2020 ◽  
Author(s):  
Qingyuan Feng ◽  
Xuzhao Bian ◽  
Xuan Liu ◽  
Ying Wang ◽  
Huiting Zhou ◽  
...  
Keyword(s):  
Cell Death ◽  
Western Blot ◽  
Cancer Cell ◽  
Malignant Tumors ◽  
Arginine Deiminase ◽  
Immunofluorescent Staining ◽  
Apoptosis Pathway ◽  
P53 Expression ◽  
Cancer Cell Death ◽  
Arginine Deprivation

Abstract Background Based on its low toxicity, arginine starvation therapy has the potential to treat those malignant tumors that can’t be treated by surgery. Arginine deiminase (ADI; EC 3.5.3.6) gene is indicated to be an ideal cancer-suppressor gene. ADI expressed in cytosol displayed higher oncolytic efficiency than ADI-PEG20 (Pegylated Arginine Deiminase by PEG 20,000)[1]. However, it is still unknown whether cytosolic ADI has the same function mechanism as ADI-PEG20 or other underlying mechanisms in cells. Methods The interaction of ADI and other protein factors was screened by yeast hybrid, and verified by co-immunoprecipitation and immunofluorescent staining. The effect of ADI inhibiting ferritin light-chain domain (FTL) on mitochondria damage was evaluated by site-directed mutation and flow cytometry. The apoptosis pathway of mitochondria control was analyzed by Western Blot and real-time PCR. The effect of p53 expression on cancer cell death was assessed by siTP53 transfection. The chromatin autophagy was explored by immunofluorescent staining and Western Blot. Results ADI expressed in cytosol inhibited the activity of cytosolic ferritin through interacting with FTL. The inactive mutant of ADI still aroused the apoptosis of some cells through mitochondria damage. Arginine deprivation also induced the expression increase of p53 and p53AIP1, which aggravated cellular mitochondria damage. Chromatin autophagy appeared at the later stage of arginine deprivation. DNA damage came along with the whole process of arginine starvation. Histone 3 (H3) was found in autophagosomes, which implied that cancer cells try to utilize the arginine in histones to survive during arginine starvation. Conclusions Mitochondria damage is the major mechanism for ADI expressed in cytosol to induce cancer cell death. Chromatophagy accumulation not only drives cancer cell to utilize histone arginine but also speeds up cancer cell death at the later time point of arginine deprivation.

scholarly journals Intracellular expression of arginine deiminase activates the mitochondrial apoptosis pathway by inhibiting cytosolic ferritin and inducing chromatin autophagy

2020 ◽  
Author(s):  
Qingyuan Feng ◽  
Xuzhao Bian ◽  
Xuan Liu ◽  
Ying Wang ◽  
Huiting Zhou ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Western Blotting ◽  
Mitochondrial Damage ◽  
Arginine Deiminase ◽  
Immunofluorescent Staining ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
P53 Expression ◽  
Mitochondrial Apoptosis Pathway

Abstract Background: Based on its low toxicity, arginine starvation therapy has the potential to cure malignant tumors that cannot be treated surgically. The Arginine deiminase (ADI) gene has been identified to be an ideal cancer-suppressor gene. ADI expressed in the cytosol displays higher oncolytic efficiency than ADI-PEG20 (Pegylated Arginine Deiminase by PEG 20,000). However, it is still unknown whether cytosolic ADI has the same mechanism of action as ADI-PEG20 or other underlying cellular mechanisms. Methods: The interactions of ADI with other protein factors were screened by yeast hybrids, and verified by co-immunoprecipitation and immunofluorescent staining. The effect of ADI inhibiting the ferritin light-chain domain (FTL) in mitochondrial damage was evaluated by site-directed mutation and flow cytometry. Control of the mitochondrial apoptosis pathway was analyzed by Western Blotting and real-time PCR experiments. The effect of p53 expression on cancer cells death was assessed by siTP53 transfection. Chromatin autophagy was explored by immunofluorescent staining and Western Blotting. Results: ADI expressed in the cytosol inhibited the activity of cytosolic ferritin by interacting with FTL. The inactive mutant of ADI still induced apoptosis in certain cell lines of ASS- through mitochondrial damage. Arginine starvation also generated an increase in the expression of p53 and p53AIP1, which aggravated the cellular mitochondrial damage. Chromatin autophagy appeared at a later stage of arginine starvation. DNA damage occurred along with the entire arginine starvation process. Histone 3 (H3) was found in autophagosomes, which implies that cancer cells attempted to utilize the arginine present in histones to survive during arginine starvation. Conclusions: Mitochondrial damage is the major mechanism of cell death induced by cytosolic ADI. The process of chromatophagy does not only stimulate cancer cells to utilize histone arginine but also speeds up cancer cell death at a later stage of arginine starvation.

scholarly journals Intracellular expression of arginine deiminase activates the mitochondrial apoptosis pathway by inhibiting cytosolic ferritin and inducing chromatin autophagy

2020 ◽  
Author(s):  
Qingyuan Feng ◽  
Xuzhao Bian ◽  
Xuan Liu ◽  
Ying Wang ◽  
Huiting Zhou ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Western Blotting ◽  
Mitochondrial Damage ◽  
Arginine Deiminase ◽  
Immunofluorescent Staining ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
P53 Expression ◽  
Mitochondrial Apoptosis Pathway

Abstract Background ： Based on its low toxicity, arginine starvation therapy has the potential to cure malignant tumors that cannot be treated surgically. The Arginine deiminase (ADI) gene has been identified to be an ideal cancer-suppressor gene. ADI expressed in the cytosol displays higher oncolytic efficiency than ADI-PEG20 (Pegylated Arginine Deiminase by PEG 20,000). However, it is still unknown whether cytosolic ADI has the same mechanism of action as ADI-PEG20 or other underlying cellular mechanisms. Methods: The interactions of ADI with other protein factors were screened by yeast hybrids, and verified by co-immunoprecipitation and immunofluorescent staining. The effect of ADI inhibiting the ferritin light-chain domain (FTL) in mitochondrial damage was evaluated by site-directed mutation and flow cytometry. Control of the mitochondrial apoptosis pathway was analyzed by Western Blotting and real-time PCR experiments. The effect of p53 expression on cancer cells death was assessed by siTP53 transfection. Chromatin autophagy was explored by immunofluorescent staining and Western Blotting. Results: ADI expressed in the cytosol inhibited the activity of cytosolic ferritin by interacting with FTL. The inactive mutant of ADI still induced apoptosis in certain cell lines of ASS- through mitochondrial damage. Arginine starvation also generated an increase in the expression of p53 and p53AIP1, which aggravated the cellular mitochondrial damage. Chromatin autophagy appeared at a later stage of arginine starvation. DNA damage occurred along with the entire arginine starvation process. Histone 3 (H3) was found in autophagosomes, which implies that cancer cells attempted to utilize the arginine present in histones to survive during arginine starvation. Conclusions: Mitochondrial damage is the major mechanism of cell death induced by cytosolic ADI. The process of Chromatophagy does not only stimulate cancer cells to utilize histone arginine but also speeds up cancer cell death at a later stage of arginine starvation.

scholarly journals Intracellular expression of arginine deiminase activates the mitochondrial apoptosis pathway by inhibiting cytosolic ferritin and inducing chromatin autophagy

2020 ◽  
Author(s):  
Qingyuan Feng ◽  
Xuzhao Bian ◽  
Xuan Liu ◽  
Ying Wang ◽  
Huiting Zhou ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Western Blotting ◽  
Mitochondrial Damage ◽  
Arginine Deiminase ◽  
Immunofluorescent Staining ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
P53 Expression ◽  
Mitochondrial Apoptosis Pathway

Abstract Background：Based on its low toxicity, arginine starvation therapy has the potential to cure malignant tumors that cannot be treated surgically. The Arginine deiminase (ADI) gene has been identified to be an ideal cancer-suppressor gene. ADI expressed in the cytosol displays higher oncolytic efficiency than ADI-PEG20 (Pegylated Arginine Deiminase by PEG 20,000). However, it is still unknown whether cytosolic ADI has the same mechanism of action as ADI-PEG20 or other underlying cellular mechanisms.Methods: The interactions of ADI with other protein factors were screened by yeast hybrids, and verified by co-immunoprecipitation and immunofluorescent staining. The effect of ADI inhibiting the ferritin light-chain domain (FTL) in mitochondrial damage was evaluated by site-directed mutation and flow cytometry. Control of the mitochondrial apoptosis pathway was analyzed by Western Blotting and real-time PCR experiments. The effect of p53 expression on cancer cells death was assessed by siTP53 transfection. Chromatin autophagy was explored by immunofluorescent staining and Western Blotting.Results: ADI expressed in the cytosol inhibited the activity of cytosolic ferritin by interacting with FTL. The inactive mutant of ADI still induced apoptosis in certain cell lines of ASS- through mitochondrial damage. Arginine starvation also generated an increase in the expression of p53 and p53AIP1, which aggravated the cellular mitochondrial damage. Chromatin autophagy appeared at a later stage of arginine starvation. DNA damage occurred along with the entire arginine starvation process. Histone 3 (H3) was found in autophagosomes, which implies that cancer cells attempted to utilize the arginine present in histones to survive during arginine starvation. Conclusions: Mitochondrial damage is the major mechanism of cell death induced by cytosolic ADI. The process of Chromatophagy does not only stimulate cancer cells to utilize histone arginine but also speeds up cancer cell death at a later stage of arginine starvation.

An Osmium(VI) Nitride Triggers Mitochondria-induced Oncosis and Apoptosis

2022 ◽  
Author(s):  
Meng Ye ◽  
Wan-Qiong Huang ◽  
Zi-Xin Li ◽  
Chuan-Xian Wang ◽  
Tao Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Liver Cancer ◽  
Anticancer Activity ◽  
Cancer Cell ◽  
Mitochondrial Damage ◽  
Tetradentate Ligand ◽  
Liver Cancer Cell ◽  
Cancer Cell Death

We report a new osmium(VI) nitrido complex bearing a nonplanar tetradentate ligand with potent anticancer activity. It causes mitochondrial damage, which induces liver cancer cell death via oncosis and apoptosis....

scholarly journals Novel camphor-based pyrimidine derivatives induced cancer cell death through a ROS-mediated mitochondrial apoptosis pathway

RSC Advances ◽  
2019 ◽  
Vol 9 (51) ◽  
pp. 29711-29720
Author(s):  
Yan Zhang ◽  
Yunyun Wang ◽  
Yuxun Zhao ◽  
Wen Gu ◽  
Yongqiang Zhu ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cell ◽  
Mitochondrial Apoptosis ◽  
Pyrimidine Derivatives ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Cancer Cell Death ◽  
Anti Tumor Activity

A series of novel camphor-based pyrimidine derivatives were synthesized and characterized. We found the compound 3f exhibited strongest anti-tumor activity via ROS-mediated mitochondrial apoptosis pathway.

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