Metabolic reprogramming in saliva of mice treated with the environmental and tobacco carcinogen dibenzo[def, p]chrysene
Abstract The goal of this study is to develop a non-invasive approach for early detection of oral squamous cell carcinoma (OSCC) using our established mouse model that faithfully recapitulates the human disease. We present for the first time a comparative metabolomic profiling of saliva samples of t...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-11-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-80921-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846147851491475456 |
|---|---|
| author | Yuan-Wan Sun Kun-Ming Chen Cesar Aliaga Karam El-Bayoumy |
| author_facet | Yuan-Wan Sun Kun-Ming Chen Cesar Aliaga Karam El-Bayoumy |
| author_sort | Yuan-Wan Sun |
| collection | DOAJ |
| description | Abstract The goal of this study is to develop a non-invasive approach for early detection of oral squamous cell carcinoma (OSCC) using our established mouse model that faithfully recapitulates the human disease. We present for the first time a comparative metabolomic profiling of saliva samples of the tobacco smoke constituent, dibenzo[def, p]pyrene, (DB[a, l]P) vs. DMSO (control)-treated mice using an established and highly sensitive LC-MS/MS approach. DB[a, l]P was administered by topical application into the mouse oral cavity (25 µmol, 3x week for 6 weeks) and saliva was collected 24 h after the last dose of carcinogen administration. Using an untargeted metabolomics approach (negative and positive modes), we found that DB[a, l]P differentially altered several metabolites known to be involved in the carcinogenesis process when compared to DMSO. Of particular significance, we found that DB[a, l]P significantly enriched the levels of phosphatidic acid, known to bind and activate mTORC which can enhance proliferation and promote carcinogenesis. Pathway enrichment analysis revealed that DB[a, l]P altered two major lipid metabolism pathways (phospholipid biosynthesis and glycerolipid metabolism). Collectively, our results using saliva as a safe and non-invasive approach, provide additional mechanistic insights on DB[a, l]P-induced OSCC and potential biomarkers for early detection and an opportunity for cancer interception via reprogramming lipid metabolism. |
| format | Article |
| id | doaj-art-e685e8a574f742d1841d51140278c20f |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-e685e8a574f742d1841d51140278c20f2024-12-01T12:24:33ZengNature PortfolioScientific Reports2045-23222024-11-0114111010.1038/s41598-024-80921-1Metabolic reprogramming in saliva of mice treated with the environmental and tobacco carcinogen dibenzo[def, p]chryseneYuan-Wan Sun0Kun-Ming Chen1Cesar Aliaga2Karam El-Bayoumy3Department of Biochemistry and Molecular Biology, Pennsylvania State University College of MedicineDepartment of Biochemistry and Molecular Biology, Pennsylvania State University College of MedicineDepartment of Biochemistry and Molecular Biology, Pennsylvania State University College of MedicineDepartment of Biochemistry and Molecular Biology, Pennsylvania State University College of MedicineAbstract The goal of this study is to develop a non-invasive approach for early detection of oral squamous cell carcinoma (OSCC) using our established mouse model that faithfully recapitulates the human disease. We present for the first time a comparative metabolomic profiling of saliva samples of the tobacco smoke constituent, dibenzo[def, p]pyrene, (DB[a, l]P) vs. DMSO (control)-treated mice using an established and highly sensitive LC-MS/MS approach. DB[a, l]P was administered by topical application into the mouse oral cavity (25 µmol, 3x week for 6 weeks) and saliva was collected 24 h after the last dose of carcinogen administration. Using an untargeted metabolomics approach (negative and positive modes), we found that DB[a, l]P differentially altered several metabolites known to be involved in the carcinogenesis process when compared to DMSO. Of particular significance, we found that DB[a, l]P significantly enriched the levels of phosphatidic acid, known to bind and activate mTORC which can enhance proliferation and promote carcinogenesis. Pathway enrichment analysis revealed that DB[a, l]P altered two major lipid metabolism pathways (phospholipid biosynthesis and glycerolipid metabolism). Collectively, our results using saliva as a safe and non-invasive approach, provide additional mechanistic insights on DB[a, l]P-induced OSCC and potential biomarkers for early detection and an opportunity for cancer interception via reprogramming lipid metabolism.https://doi.org/10.1038/s41598-024-80921-1Tobacco and Environmental CarcinogensOral squamous cell carcinomaMouse modelSalivaMetabolic profiles |
| spellingShingle | Yuan-Wan Sun Kun-Ming Chen Cesar Aliaga Karam El-Bayoumy Metabolic reprogramming in saliva of mice treated with the environmental and tobacco carcinogen dibenzo[def, p]chrysene Scientific Reports Tobacco and Environmental Carcinogens Oral squamous cell carcinoma Mouse model Saliva Metabolic profiles |
| title | Metabolic reprogramming in saliva of mice treated with the environmental and tobacco carcinogen dibenzo[def, p]chrysene |
| title_full | Metabolic reprogramming in saliva of mice treated with the environmental and tobacco carcinogen dibenzo[def, p]chrysene |
| title_fullStr | Metabolic reprogramming in saliva of mice treated with the environmental and tobacco carcinogen dibenzo[def, p]chrysene |
| title_full_unstemmed | Metabolic reprogramming in saliva of mice treated with the environmental and tobacco carcinogen dibenzo[def, p]chrysene |
| title_short | Metabolic reprogramming in saliva of mice treated with the environmental and tobacco carcinogen dibenzo[def, p]chrysene |
| title_sort | metabolic reprogramming in saliva of mice treated with the environmental and tobacco carcinogen dibenzo def p chrysene |
| topic | Tobacco and Environmental Carcinogens Oral squamous cell carcinoma Mouse model Saliva Metabolic profiles |
| url | https://doi.org/10.1038/s41598-024-80921-1 |
| work_keys_str_mv | AT yuanwansun metabolicreprogramminginsalivaofmicetreatedwiththeenvironmentalandtobaccocarcinogendibenzodefpchrysene AT kunmingchen metabolicreprogramminginsalivaofmicetreatedwiththeenvironmentalandtobaccocarcinogendibenzodefpchrysene AT cesaraliaga metabolicreprogramminginsalivaofmicetreatedwiththeenvironmentalandtobaccocarcinogendibenzodefpchrysene AT karamelbayoumy metabolicreprogramminginsalivaofmicetreatedwiththeenvironmentalandtobaccocarcinogendibenzodefpchrysene |