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Principal xenobiotic-metabolizing enzyme systems in human head and neck squamous cell carcinoma
1Head and Neck Surgery Department, Institut Gustave-Roussy, Villejuif, France.
Abstract:
To better understand drug and carcinogen metabolism pathways in head and neck squamous cell carcinoma we assayed the principal drug- and carcinogen-metabolizing enzyme systems in both tumors and their corresponding adjacent non-tumoral tissues. Cytochromes P450 (1A1/A2, 2B1/B2, 2C8-10, 2E1, 3A4), epoxide hydrolase and glutathione S-transferases (GST-alpha, GST-mu, GST-pi) were assayed by immunoblotting. GST activity, total glutathione, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase and sulfatase, were determined by spectral assays. Results showed the absence of all probed cytochromes P450 in tumors and non-tumoral tissues, including P450 1A1/1A2 known to be involved in tobacco-related carcinogenesis. No statistical difference was noted between tumors and adjacent non-tumoral tissues for most enzymes studied (GST-alpha, GST-mu, GST-pi, GST activity, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase and sulfatase). However, total glutathione concentrations were significantly higher (P < 0.05) in tumors (47 +/- 20 nmol/mg protein) than in non-tumoral tissues (19 +/- 9). On the contrary, epoxide hydrolase was significantly less expressed in tumors (18 +/- 9 micrograms/mg protein) compared to corresponding non-tumoral tissues (37 +/- 9). These data provide new information concerning human head and neck cancer biology that could possibly have clinical implications.
Insights
Drug and carcinogen metabolism in head and neck squamous cell carcinoma revealed significantly higher total glutathione and lower epoxide hydrolase in tumors. Cytochrome P450 enzymes were absent in both tumor and non-tumoral tissues.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Head and neck squamous cell carcinoma (HNSCC) involves complex metabolic pathways.
- Understanding drug and carcinogen metabolism is crucial for HNSCC treatment and prevention.
- Key enzymes like Cytochromes P450, epoxide hydrolase, and glutathione S-transferases play vital roles.
Purpose of the Study:
- To investigate drug and carcinogen-metabolizing enzyme systems in HNSCC tumors and adjacent non-tumoral tissues.
- To identify alterations in enzyme expression and activity associated with HNSCC.
- To explore potential clinical implications of these metabolic changes.
Main Methods:
- Enzyme systems including Cytochromes P450 (CYP1A1/A2, 2B1/B2, 2C8-10, 2E1, 3A4), epoxide hydrolase, and glutathione S-transferases (GSTs) were assayed.
- Immunoblotting was used to measure enzyme protein levels.
- Spectral assays determined GST activity, total glutathione, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase activities.
Main Results:
- All probed Cytochrome P450 enzymes were absent in both tumor and non-tumoral tissues.
- No significant differences were observed for most GSTs, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase between tumors and adjacent tissues.
- Total glutathione concentrations were significantly higher in tumors (47 nmol/mg protein) compared to non-tumoral tissues (19 nmol/mg protein).
- Epoxide hydrolase expression was significantly lower in tumors (18 µg/mg protein) than in non-tumoral tissues (37 µg/mg protein).
Conclusions:
- HNSCC exhibits distinct alterations in drug and carcinogen metabolism, notably increased glutathione and decreased epoxide hydrolase.
- The absence of Cytochrome P450 enzymes in HNSCC warrants further investigation.
- These findings may offer insights into HNSCC biology and potential therapeutic strategies.