Hypericin inhibited protein kinase

Takahashi I, Nakanishi S, Kobayashi E, Nakano H, Suzuki K, Tamaoki T. (1989). Hypericin and pseudohypericin specifically inhibit protein kinase C possible relation to their antiretroviral activity. Biochem Biophys Res Common. 165(3) 1207-12. 

Like hypericin the E. exhibit photodynamic activity and inhibit protein kinase C. The E. exist in solution as tautomeric mixtures, some E. can be separated into diastereomeric pairs. On account of their helical chirality, some E. exhibit very high optical rotation. 

Agostinis P, Vandenbogaerde A, Donella-Deana A, Pinna LA, Lee KT, Goris J, Merlevede W, Vandenheede JR, De Witte P. (1995). Photosensitized inhibition of growth factor-regulated protein kinases by hypericin. Biochem Pharmacol. 49(11) 1615-22. 

Harris MS, Sakamoto T, Kimura H, He S, Spee C, Gopalakrishna R, Gundimeda U, Yoo JS, Hinton DR, Ryan SJ. (1996). Hypericin inhibits cell growth and induces apoptosis in retinal pigment epithelial cells possible involvement of protein kinase C. Curr Eye Res. 15(3) 255-62. 

Zhang W, Law RE, Hinton DR, Couldwell WT. (1997). Inhibition of human malignant glioma cell motility and invasion in vitro by hypericin, a potent protein kinase C inhibitor. Cancer Lett. 120(1) 31-8. 

In addition, some Authors suggested that the antiretroviral efficacy of hypericin is associated with the inhibition of protein-kinase C-mediated phosphorylation, occurring during the viral infection of the cells [10]. 

Following detection of the antiviral activity of hypericin 1 (see above), a number of observations have suggested that this compound may as well represent a potential anti-cancer therapy. These biological properties include the light-dependent inhibition of protein kinase C [142], the photosensitized inhibition of mitochondrial succinoxidase [143], and the photoinduced inhibition of epidermal growth factor receptor (EGF-R) tyrosine kinase activity [144]. 

Inhibition of EGF-R tyrosine kinase by hypericin 1 was shown to be irreversible, non-competitive and time as well as temperature dependent. The IC50 increased from 0.75 pM in the dark to 44 nM with light illumination for 30 min. This effect was presumably due to a type I photosensitization mechanism since exclusion of oxygen did not alter the inhibition curve. Some Ser/Thr protein kinases (e.g., protein kinase A, casein kinase 1 and 2) and the enzyme 5 -nucleotidase were not inhibited even at concentrations > 100 pM [144]. However, the same authors recently reported that hypericin 1 in addition to protein kinase C also caused the light-dependent inhibition of certain other Ser/Thr kinases (e.g. protein kinase CK-2, mitogen-activated kinase) and the insulin receptor tyrosine kinase, while it was ineffective towards the cytosolic tyrosine kinases Lyn, Fgr, TPK-IIB and CSK. These results suggest that distantly related protein kinases could still share common reactive domains for the interaction with hypericin 1 [156]. In contrast to the above mentioned studies, Richter and Davies [157] observed no inhibition of EGF-induced tyrosine phosphorylation of the EGF-R in HN5 squamous carcinoma... 

---