SIRT1-activating butein inhibits arecoline-induced mitochondrial dysfunction through PGC1α and MTP18 in oral cancer
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Bishnu Prasad Behera
- Soumya Ranjan Mishra
- Kewal Kumar Mahapatra
- Shankargouda Patil
- Thomas Efferth
- Sujit Kumar Bhutia
- DOI
- 10.1016/j.phymed.2024.155511
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine
- Sprache
- en
- Artikelnummer
- 155511
- Paginierung
- 155511 - 155511
- Datum der Veröffentlichung
- 2024
- Status
- Accepted
- Herausgeber
- Elsevier BV
- Herausgeber URL
- http://dx.doi.org/10.1016/j.phymed.2024.155511
- Datum der Datenerfassung
- 2024
- Titel
- SIRT1-activating butein inhibits arecoline-induced mitochondrial dysfunction through PGC1α and MTP18 in oral cancer
- Ausgabe der Zeitschrift
- 129
Data source: Crossref
- Other metadata sources:
-
- Abstract
- <h4>Background</h4>Mitochondrial dysfunction associated with mitochondrial DNA mutations, enzyme defects, generation of ROS, and altered oxidative homeostasis is known to induce oral carcinogenesis during exposure to arecoline. Butein, a natural small molecule from Butea monosperma, possesses anti-inflammatory, anti-diabetic, and anti-cancer effects. However, the role of butein in the mitochondrial quality control mechanism has not been illuminated clearly.<h4>Purpose</h4>This study aimed to explore the role of butein in preserving mitochondrial quality control during arecoline-induced mitochondrial dysfunction in oral cancer to curtail the early onset of carcinogenesis.<h4>Methods</h4>Cell viability was evaluated by MTT assay. The relative protein expressions were determined by western blotting. Immunofluorescence and confocal imaging were used to analyze the relative fluorescence and co-localization of proteins. Respective siRNAs were used to examine the knockdown-based studies.<h4>Results</h4>Butein, in the presence of arecoline, significantly caused a decrease in mitochondrial hyperpolarization and ROS levels in oral cancer cells. Mechanistically, we found an increase in COXIV, TOM20, and PGC1α expression during butein treatment, and inhibition of PGC1α blunted mitochondrial biogenesis and decreased the mitochondrial pool. Moreover, the fission protein MTP18, and its molecular partners DRP1 and MFF were dose-dependently increased during butein treatment to maintain mitochondria mass. In addition, we also found increased expression of various mitophagy proteins, including PINK1, Parkin, and LC3 during butein treatment, suggesting the clearance of damaged mitochondria to maintain a healthy mitochondrial pool. Interestingly, butein increased the activity of SIRT1 to enhance the functional mitochondrial pool, and inhibition of SIRT1 found to reduce the mitochondrial levels, as evident from the decrease in the expression of PGC1α and MTP18 in oral cancer cells.<h4>Conclusion</h4>Our study proved that SIRT1 maintains a functional mitochondrial pool through PGC1α and MTP18 for biogenesis and fission of mitochondria during arecoline exposure and could decrease the risk of mitochondria dysfunctionality associated with the onset of oral carcinogenesis.
- Addresses
- Cancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Sundergarh, 769008, Odisha, India.
- Autoren
- Bishnu Prasad Behera
- Soumya Ranjan Mishra
- Kewal Kumar Mahapatra
- Shankargouda Patil
- Thomas Efferth
- Sujit Kumar Bhutia
- DOI
- 10.1016/j.phymed.2024.155511
- eISSN
- 1618-095X
- Externe Identifier
- PubMed Identifier: 38723523
- Funding acknowledgements
- Department of Atomic Energy, Government of India:
- Department of Science and Technology, Ministry of Science and Technology, India:
- Board of Research in Nuclear Sciences: 54/14/07/2022-BRNS/10913
- Science and Engineering Research Board: CRG/2021/000053
- Open access
- false
- ISSN
- 0944-7113
- Zeitschrift
- Phytomedicine : international journal of phytotherapy and phytopharmacology
- Schlüsselwörter
- Cell Line, Tumor
- Mitochondria
- Humans
- Mouth Neoplasms
- Reactive Oxygen Species
- Chalcones
- Arecoline
- Cell Survival
- Sirtuin 1
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2024
- Paginierung
- 155511
- Datum der Veröffentlichung
- 2024
- Status
- Published online
- Datum der Datenerfassung
- 2024
- Titel
- SIRT1-activating butein inhibits arecoline-induced mitochondrial dysfunction through PGC1α and MTP18 in oral cancer.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 129
Data source: Europe PubMed Central
- Abstract
- BACKGROUND: Mitochondrial dysfunction associated with mitochondrial DNA mutations, enzyme defects, generation of ROS, and altered oxidative homeostasis is known to induce oral carcinogenesis during exposure to arecoline. Butein, a natural small molecule from Butea monosperma, possesses anti-inflammatory, anti-diabetic, and anti-cancer effects. However, the role of butein in the mitochondrial quality control mechanism has not been illuminated clearly. PURPOSE: This study aimed to explore the role of butein in preserving mitochondrial quality control during arecoline-induced mitochondrial dysfunction in oral cancer to curtail the early onset of carcinogenesis. METHODS: Cell viability was evaluated by MTT assay. The relative protein expressions were determined by western blotting. Immunofluorescence and confocal imaging were used to analyze the relative fluorescence and co-localization of proteins. Respective siRNAs were used to examine the knockdown-based studies. RESULTS: Butein, in the presence of arecoline, significantly caused a decrease in mitochondrial hyperpolarization and ROS levels in oral cancer cells. Mechanistically, we found an increase in COXIV, TOM20, and PGC1α expression during butein treatment, and inhibition of PGC1α blunted mitochondrial biogenesis and decreased the mitochondrial pool. Moreover, the fission protein MTP18, and its molecular partners DRP1 and MFF were dose-dependently increased during butein treatment to maintain mitochondria mass. In addition, we also found increased expression of various mitophagy proteins, including PINK1, Parkin, and LC3 during butein treatment, suggesting the clearance of damaged mitochondria to maintain a healthy mitochondrial pool. Interestingly, butein increased the activity of SIRT1 to enhance the functional mitochondrial pool, and inhibition of SIRT1 found to reduce the mitochondrial levels, as evident from the decrease in the expression of PGC1α and MTP18 in oral cancer cells. CONCLUSION: Our study proved that SIRT1 maintains a functional mitochondrial pool through PGC1α and MTP18 for biogenesis and fission of mitochondria during arecoline exposure and could decrease the risk of mitochondria dysfunctionality associated with the onset of oral carcinogenesis.
- Date of acceptance
- 2024
- Autoren
- Bishnu Prasad Behera
- Soumya Ranjan Mishra
- Kewal Kumar Mahapatra
- Shankargouda Patil
- Thomas Efferth
- Sujit Kumar Bhutia
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/38723523
- DOI
- 10.1016/j.phymed.2024.155511
- eISSN
- 1618-095X
- Zeitschrift
- Phytomedicine
- Schlüsselwörter
- Butein
- Carcinogenesis
- MTP18
- Mitochondrial pool
- Oral cancer
- PGC1α
- SIRT1
- Humans
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
- Mouth Neoplasms
- Mitochondria
- Arecoline
- Cell Line, Tumor
- Reactive Oxygen Species
- Chalcones
- Sirtuin 1
- Cell Survival
- Sprache
- eng
- Country
- Germany
- Paginierung
- 155511
- PII
- S0944-7113(24)00175-2
- Datum der Veröffentlichung
- 2024
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2024
- Titel
- SIRT1-activating butein inhibits arecoline-induced mitochondrial dysfunction through PGC1α and MTP18 in oral cancer.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 129
Data source: PubMed
- Beziehungen:
-