This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
qianqian chen
Shanghai Tenth People's Hospital
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Berberine (BBR), as an isoquinoline alkaloid, is commonly utilized in traditional Chinese medicine. Previous studies have proven that BBR possesses potential anti-tumor effect. However, the mechanism of on mitochondrial function in anti-NSCLC are still unknown.
Methods
Cell Counting Kit-8 (CCK-8), flow cytometry and western blotting were utilized to characterize the roles and relationships among BBR, ROS, ASK1, JNK, coxIV,
caspase-3, cytochrome c ,bcl-2 and bax in NSCLC. Immunohistochemical (IHC) analysis was built to examine their expression in vivo.
Results
In this study, we found that BBR potently suppressed NSCLC cells (A549 and PC9) growth by inducing apoptosis in a dose- and time-dependent manner. BBR induced apoptosis in NSCLC as evidenced by caspase-3 cleavage, cytochrome c release, and mitochondrial membrane depolarization. Furthermore, BBR induced ROS generation and ASK1 and JNK activation. To explore whether such apoptosis was linked to ROS production and ASK1 and JNK activation, we treated cells with a JNK inhibitor (SP600125), which significantly suppressed BBR-induced apoptosis. We further found that treating these cells with the anti-oxidant N-acetyl cysteine (NAC) was sufficient to both suppress ASK1 and JNK activation and to disrupt apoptotic induction.
Conclusions
Together, these data suggest that BBR induces NSCLC cells apoptosis via ROS-mediated ASK1/JNK and mitochondrial pathway activation.
Keywords
Berberine, Apoptosis, Mitochondria, ROS, NSCLC
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 05 Oct, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Health Economics & Outcomes Research
Learn more about our company.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
qianqian chen
Shanghai Tenth People's Hospital
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 05 Oct, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Health Economics & Outcomes Research
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Berberine (BBR), as an isoquinoline alkaloid, is commonly utilized in traditional Chinese medicine. Previous studies have proven that BBR possesses potential anti-tumor effect. However, the mechanism of on mitochondrial function in anti-NSCLC are still unknown.
Methods
Cell Counting Kit-8 (CCK-8), flow cytometry and western blotting were utilized to characterize the roles and relationships among BBR, ROS, ASK1, JNK, coxIV,
caspase-3, cytochrome c ,bcl-2 and bax in NSCLC. Immunohistochemical (IHC) analysis was built to examine their expression in vivo.
Results
In this study, we found that BBR potently suppressed NSCLC cells (A549 and PC9) growth by inducing apoptosis in a dose- and time-dependent manner. BBR induced apoptosis in NSCLC as evidenced by caspase-3 cleavage, cytochrome c release, and mitochondrial membrane depolarization. Furthermore, BBR induced ROS generation and ASK1 and JNK activation. To explore whether such apoptosis was linked to ROS production and ASK1 and JNK activation, we treated cells with a JNK inhibitor (SP600125), which significantly suppressed BBR-induced apoptosis. We further found that treating these cells with the anti-oxidant N-acetyl cysteine (NAC) was sufficient to both suppress ASK1 and JNK activation and to disrupt apoptotic induction.
Conclusions
Together, these data suggest that BBR induces NSCLC cells apoptosis via ROS-mediated ASK1/JNK and mitochondrial pathway activation.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Loading...