Back to Search
Start Over
In vitro simulation of the liver first-pass effect with biotransformation-competent HepG2 cells to study effects of MG-132 on liver and cancer cells.
- Source :
-
Clinical Hemorheology & Microcirculation . 2024, Vol. 86 Issue 1/2, p159-168. 10p. - Publication Year :
- 2024
-
Abstract
- BACKGROUND: Liver biotransformation is the major route for drug metabolism in humans, often catalysed by cytochrome P450 (CYP) enzymes. This first-pass effect can lead to hepatotoxicity and influences the bioavailability of drugs. OBJECTIVE: We aimed to establish in vitro culture systems simulating the liver first-pass to study effects of the proteasome inhibitor MG-132 simultaneously on hepatocytes and cancer cells. METHODS: The first-pass effect was simulated by conditioned medium transfer (CMT) from pre-treated HepG2 CYP3A4-overexpressing cells to either pancreatic cancer cell line PANC-1 or primary colon cancer cells, and by indirect co-culture (CC) of liver and cancer cells in a shared medium compartment. Experimental proteasome inhibitor MG-132 was used as test substance as it is detoxified by CYP3A4. RESULTS: Cancer cells showed higher viabilities in the first-pass simulation by CMT and CC formats when compared to monocultures indicating effective detoxification of MG-132 by HepG2 CYP3A4-overexpressing cells. HepG2-CYP3A4 cells showed reduced viabilites after treatment with MG-132. CONCLUSIONS: We successfully established two different culture systems to simulate the liver first-pass effect in vitro. Such systems easily allow to study drug effects simultaneously on liver and on target cancer cells. They are of great value in pre-clinical cancer research, pharmaceutical research and drug development. [ABSTRACT FROM AUTHOR]
- Subjects :
- *LIVER cells
*CANCER cells
*LIVER cancer
*LIVER
*DRUG bioavailability
Subjects
Details
- Language :
- English
- ISSN :
- 13860291
- Volume :
- 86
- Issue :
- 1/2
- Database :
- Academic Search Index
- Journal :
- Clinical Hemorheology & Microcirculation
- Publication Type :
- Academic Journal
- Accession number :
- 175644969
- Full Text :
- https://doi.org/10.3233/CH-238108