scholarly journals Sesquiterpene from Polygonum Barbatum Disrupt Mitochondrial Membrane Potential to Induce Apoptosis and Inhibits Metastasis by Downregulating Matrix Metalloproteinase and Osteopontin in NCI-H460 Cells

2021 ◽  
Author(s):  
Binte Zehra ◽  
Ayaz Ahmed ◽  
Ajmal Khan ◽  
Afshan Shams ◽  
Reaz Uddin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Membrane Potential ◽  
Matrix Metalloproteinase ◽  
Molecular Mechanism ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Matrix Metalloproteinase 2 ◽  
Invasion Assay ◽  
Cancer Management ◽  
H460 Cells

Abstract Background: Globally, lung cancer accounts for 18% of cancer-associated mortalities. Among the subtypes, non-small-cell lung cancer (NSCLC) is the most prevalent one. The increased resistance and poor survival rates, signifies disease aggressiveness and thus require a search for an alternative anticancer molecule. Hypothesis/Purpose: Earlier, the isolated sesquiterpene i.e. compound 1 ((E)-Methyl 6-acetoxy-7-methoxy-1-(2-methylpropylidene)-1H-indene-3-carboxylate) from P. barbatum was isolated, characterized by us and reported for preliminary anticancer activity. Considering its potent activity, this study was designed to explore the underlying molecular mechanism of apoptosis and metastasis against NCI-H460 cells. Method: The molecular mechanism of compound 1 inducing apoptosis and inhibiting metastasis was elucidated by analyzing mitochondrial membrane potential, DNA fragmentation, clonogenic assay, invasion assay and expression of apoptotic (Caspases 3, 6, 8, 9 and BAK) and metastatic markers (MMP 2, 9 and osteopontin). Results: Compound 1 significantly inhibited cell proliferation and induced apoptosis via intrinsic route i.e. the mitochondrial pathway by disrupting mitochondrial membrane potential. The enhanced expression of caspases 6, 9, BAK and HRK with downregulation of Bcl-2L1 and Ki67 further confirmed the involvement of the intrinsic apoptotic pathway. Moreover, compound 1 restricted the invasive nature of NCI-H460 cells evinced by reduced cell invasion in Boyden chamber invasion assay and downregulating the expression of metastatic markers i.e. matrix metalloproteinase 2 / 9 and VEGF. It was also found that it blocks osteopontin by negatively regulating its expression; a marker protein in cancer management. Conclusion: Conclusively, this sesquiterpene exhibited potent anticancer and anti-metastatic activity and can be explored further as possible pharmacophores

scholarly journals In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer

Nature ◽  
2019 ◽  
Vol 575 (7782) ◽  
pp. 380-384 ◽  
Author(s):  
Milica Momcilovic ◽  
Anthony Jones ◽  
Sean T. Bailey ◽  
Christopher M. Waldmann ◽  
Rui Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Membrane Potential ◽  
Small Cell Lung Cancer ◽  
Mitochondrial Membrane Potential ◽  
Cell Lung Cancer ◽  
In Vivo Imaging ◽  
Mitochondrial Membrane ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Emodin, isolated and characterized from an endophytic fungus Polyporales sp., induces apoptotic cell death in human lung cancer cells through the loss of mitochondrial membrane potential

2017 ◽  
Vol 6 (5) ◽  
pp. 288-292
Author(s):  
Refaz Ahmad Dar ◽  
◽  
Rabiya Majeed ◽  
Abid Ali sheikh ◽  
Shakeel-u Rehman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Membrane Potential ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Endophytic Fungus ◽  
Mitochondrial Membrane ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Close Relative ◽  
Dependent Manner

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a Chinese herbal anthraquinone that exhibits numerous biological activities, such as antitumor, antibacterial, antiinflammatory, and immunosuppressive. From an endophytic fungus, a close relative of Polyporales sp., found in association with Rheum emodi, Wall. ex Meissn a compound (Rz) was isolated and characterizedby different spectroscopic techniques (1H-NMR, 13CNMR, 2D-NMR, and HRMS). The compound (Rz) displayed a range of cytotoxicities against different human cancer cell lines like THP-1(Leukemia), A549 (Lung), NCI-H322 (lung) and Colo-205(colon) at a concentration of 70 and 100 µM. The compound had strong anticancer activity by arresting the cell cycle at G1 and G2/M phase and loss of mitochondrial membrane potential in A-549 lung cancer cells in concentration dependent manner. The study suggests that emodin induced anticancer effects may have novel therapeutic applications for the treatment of lung cancer.

scholarly journals Apoptosis Effect of Girinimbine Isolated fromMurraya koenigiion Lung Cancer CellsIn Vitro

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Syam Mohan ◽  
Siddig Ibrahim Abdelwahab ◽  
Shiau-Chuen Cheah ◽  
Mohd Aspollah Sukari ◽  
Suvitha Syam ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Membrane Potential ◽  
Cytochrome C ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Annexin V ◽  
Murraya Koenigii ◽  
Plasma Membrane Permeability ◽  
Lysosomal Stability

Murraya koenigiiSpreng has been traditionally claimed as a remedy for cancer. The current study investigated the anticancer effects of girinimbine, a carbazole alkaloid isolated fromMurraya koenigiiSpreng, on A549 lung cancer cells in relation to apoptotic mechanistic pathway. Girinimbine was isolated fromMurraya koenigiiSpreng. The antiproliferative activity was assayed using MTT and the apoptosis detection was done by annexin V and lysosomal stability assays. Multiparameter cytotoxicity assays were performed to investigate the change in mitochondrial membrane potential and cytochrome c translocation. ROS, caspase, and human apoptosis proteome profiler assays were done to investigate the apoptotic mechanism of cell death. The MTT assay revealed that the girinimbine induces cell death with an IC50of 19.01 μM. A significant induction of early phase of apoptosis was shown by annexin V and lysosomal stability assays. After 24 h treatment with 19.01 μM of girinimbine, decrease in the nuclear area and increase in mitochondrial membrane potential and plasma membrane permeability were readily visible. Moreover the translocation of cytochrome c also was observed. Girinimbine mediates its antiproliferative and apoptotic effects through up- and downregulation of apoptotic and antiapoptotic proteins. There was a significant involvement of both intrinsic and extrinsic pathways. Moreover, the upregulation of p53 as well as the cell proliferation repressor proteins, p27 and p21, and the significant role of insulin/IGF-1 signaling were also identified. Moreover the caspases 3 and 8 were found to be significantly activated. Our results taken together indicated that girinimbine may be a potential agent for anticancer drug development.

scholarly journals Influenza Virus Protein PB1-F2 Inhibits the Induction of Type I Interferon by Binding to MAVS and Decreasing Mitochondrial Membrane Potential

2012 ◽  
Vol 86 (16) ◽  
pp. 8359-8366 ◽  
Author(s):  
Zsuzsanna T. Varga ◽  
Alesha Grant ◽  
Balaji Manicassamy ◽  
Peter Palese
Keyword(s):  
Influenza Virus ◽  
Membrane Potential ◽  
Molecular Mechanism ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Transmembrane Domain ◽  
Type I Interferon ◽  
Adaptor Protein ◽  
Type I ◽  
Dependent Manner

PB1-F2 is a small, 87- to 90-amino-acid-long protein encoded by the +1 alternate open reading frame of the PB1 gene of most influenza A virus strains. It has been shown to contribute to viral pathogenicity in a host- and strain-dependent manner, and we have previously discovered that a serine at position 66 (66S) in the PB1-F2 protein increases virulence of the 1918 and H5N1 pandemic viruses. Recently, we have shown that PB1-F2 inhibits the induction of type I interferon (IFN) at the level of the MAVS adaptor protein. However, the molecular mechanism for the IFN antagonist function of PB1-F2 has remained unclear. In the present study, we demonstrated that the C-terminal portion of the PB1-F2 protein binds to MAVS in a region that contains the transmembrane domain. Strikingly, PB1-F2 66S was observed to bind to MAVS more efficiently than PB1-F2 66N. We also tested the effect of PB1-F2 on the IFN antagonist functions of the polymerase proteins PB1, PB2, and PA and observed enhanced IFN inhibition by the PB1 and PB2 proteins in combination with PB1-F2 but not by the PA protein. Using a flow cytometry-based assay, we demonstrate that the PB1-F2 protein inhibits MAVS-mediated IFN synthesis by decreasing the mitochondrial membrane potential (MMP). Interestingly, PB1-F2 66S affected the MMP more efficiently than wild-type PB1-F2. In summary, the results of our study identify the molecular mechanism by which the influenza virus PB1-F2 N66S protein increases virulence.

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