Hypericin, a potential new BH3 mimetic.

Many types of cancer such as prostate cancer, myeloid leukemia, breast cancer, glioblastoma display strong chemo resistance, which is supported by enhanced expression of multiple anti-apoptotic Bcl-2, Bcl-XL and Mcl-1 proteins. The viable anti-cancer strategies are based on developing anti-apoptotic Bcl-2 proteins inhibitors, BH3 mimetics. Our focus in past years has been on the investigating a new potential BH3 mimetic, Hypericin (Hyp).

Searching for combination therapy by clustering methods: Stimulation of PKC in Golgi apparatus combined with hypericin induced PDT.

Cancer cell metabolism is a very attractive target for anticancer treatments. This work focuses on protein kinase C (PKC) signaling in the U87 MG glioma. By means of western blot, fluorescence and time-resolved fluorescence microscopy the correlation between the Golgi apparatus (GA), lysosomes and mitochondria were evaluated.

Importance of Hypericin-Bcl2 interactions for biological effects at subcellular levels.

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.

Inhibition of amyloid fibril formation and disassembly of pre-formed fibrils by natural polyphenol rottlerin.

Natural polyphenols, curcumin, rottlerin and EGCG were selected for initial computational modeling of protein-ligand interaction patterns. The docking calculations demonstrated that these polyphenols can easily adjust their conformational shape to fit well into the binding sites of amyloidogenic proteins. The experimental part of the study focused on the effect of rottlerin on fibrillation of three distinct amyloidogenic proteins, namely insulin, lysozyme and Aβ peptide.

In vitro identification of mitochondrial oxidative stress production by time-resolved fluorescence imaging of glioma cells.

Oxidative phosphorylation and glycolysis are important features, by which cells could bypass oxidative stress. The level of oxidative stress, and the ability of cells to promote oxidative phosphorylation or glycolysis, significantly determined proliferation or cell demise. In the present work, we have employed selective mitochondrial probe MitoTracker™ Orange CMTM/Ros (MTO) to estimate the level of oxidative stress in cancer cells at different stressed conditions.