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Inhibition of mouse skin protein kinase C by benzoyl peroxide
1Department of Dermatology, University of Illinois, College of Medicine, Chicago 60612.
Abstract:
Benzoyl peroxide (BP), used widely in dermatologic therapy and by the food industry, is considered a tumor promoter in chemically induced skin. Tumor promoters of both the phorbol and non-phorbol type interact with protein kinase C (PKC). This enzyme, therefore, is regarded as the intracellular receptor for a number of tumor promoters. BP bears some structural resemblance to diacylglycerol (DAG) and thus may exert its action through the PKC system. Based on these observations, we have investigated the effect of BP on PKC from mouse skin. Our data show that unlike phorbol esters, which stimulate PKC (in vivo and in vitro), BP inhibits PKC. Concentration-dependent inhibition by BP is observed when PKC is stimulated by phorbol esters, diacylglycerol, phosphatidyl serine (PS), or a combination of the latter two. BP also inhibits PKC stimulated by (-) Indolactam V, a nonphorbol compound resembling the teleocidins. 3H-phorbol ester binding experiments reveal that inhibition by BP may be due to its interference with the phorbol ester binding site and consequently diacylglycerol binding. The binding data and the inability of BP to inhibit either cyclic AMP-dependent protein kinase I or II imply that BP interacts with PKC, and not with the histone substrate. Results presented here clearly indicate that unlike phorbol and certain non-phorbol type of tumor promoters BP does not stimulate PKC in vitro.
Insights
Benzoyl peroxide (BP) inhibits protein kinase C (PKC), a key enzyme in tumor promotion, unlike other tumor promoters. This suggests a novel mechanism for BP
Area of Science:
- Biochemistry
- Dermatology
- Cancer Research
Background:
- Benzoyl peroxide (BP) is widely used in dermatology and the food industry.
- BP is recognized as a tumor promoter in chemically induced skin conditions.
- Tumor promoters, including phorbol and non-phorbol types, interact with protein kinase C (PKC).
Purpose of the Study:
- To investigate the effect of Benzoyl peroxide (BP) on protein kinase C (PKC) from mouse skin.
- To determine if BP interacts with the PKC system, similar to other tumor promoters.
- To elucidate the mechanism by which BP influences PKC activity.
Main Methods:
- In vitro assays measuring PKC activity.
- Concentration-dependent inhibition studies using various PKC activators (phorbol esters, diacylglycerol, phosphatidyl serine).
- 3H-phorbol ester binding experiments to assess interaction with the phorbol ester binding site.
Main Results:
- Benzoyl peroxide (BP) was found to inhibit, rather than stimulate, protein kinase C (PKC) activity.
- BP demonstrated concentration-dependent inhibition of PKC stimulated by phorbol esters, diacylglycerol, and phosphatidyl serine.
- Binding studies indicated that BP may interfere with the phorbol ester and diacylglycerol binding sites on PKC.
Conclusions:
- Benzoyl peroxide (BP) inhibits protein kinase C (PKC) in vitro, a mechanism distinct from phorbol ester and non-phorbol tumor promoters.
- BP's inhibition of PKC may occur through interference with its binding sites for activators like phorbol esters and diacylglycerol.
- These findings suggest a unique mode of action for BP in the context of tumor promotion via the PKC pathway.