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- W2967572387 abstract "Hypericin (Hyp) is a naturally occurring compound used as photosensitizer in photodynamic therapy and diagnosis. Recently, we have shown that Hyp presence alone, without illumination, resulted in substantial biological effects at several sub-cellular levels. Hyp induced changes in cellular ultrastructure, mitochondria function and metabolism, and distribution of Bcl2 proteins in malignant and non-malignant cells. The molecular mechanisms that underlie Hyp light-independent effects are still elusive. We have hypothesized that Bcl2-Hyp interactions might be one possible mechanism. We performed molecular docking studies to determine the Hyp-Bcl2 interaction profile. Based on the interaction profiles small Bcl2 peptide segments were selected for further study. We designed small peptides corresponding to Bcl2 BH3 and BH1 domains and tested the binding of Hyp and Bcl2 known inhibitor, ABT263, to the peptides in computer modeling and in vitro binding studies. We employed endogenous tryptophan and tyrosine in the BH3 and BH1 peptides, respectively, and their fluorescent properties to show interaction with Hyp and ABT263. Overall, our results indicate that Hyp can interact with Bcl2 protein at its BH3-BH1 hydrophobic groove, and this interaction may trigger changes in intracellular distribution of Bcl2 proteins. In addition, our computer modeling results suggest that Hyp also interacts with other anti-apoptotic members of Bcl2 family similar to the known BH3 mimetics. Our findings are novel and might contribute to understanding Hyp light-independent effects. In addition, they may substantiate the therapeutic use of Hyp as a BH3 mimetic molecule to enhance other cancer treatments." @default.
- W2967572387 created "2019-08-22" @default.
- W2967572387 creator A5041840931 @default.
- W2967572387 creator A5064261876 @default.
- W2967572387 creator A5064519824 @default.
- W2967572387 creator A5085113005 @default.
- W2967572387 date "2019-12-01" @default.
- W2967572387 modified "2023-09-27" @default.
- W2967572387 title "Importance of Hypericin-Bcl2 interactions for biological effects at subcellular levels" @default.
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