Antitumor activities of hypericin as a protein tyrosine kinase blocker

Naphtodianthrone hypericin produced a potent antitumor activityin vitro against several tumor cells. However, it did not show any cytotoxicity on normal cells such asMacaccus rheus monkey kidney cells (MA-104) and primary cultured rat hepatocytes up to 500 μM concentration. Hypericin added to A431 human epidermoid carcinoma cell membrane inhibited the autophosphorylation of the epidermal growth factor (EGF) receptor and the tyrosine phosphorylation of RR-SRC peptide catalyzed by an EGF-receptor. Similarly, treatment of the A431 cells with hypericin inhibited the tyrosine phosphorylation of EGF-dependent endogenous EGF-receptor by western blotting analysis. Hypericin also inhibited the T cell PTK, P56 ^lck , in a dose-dependent fashion with an IC₅₀=5 μM. The tyrosine phosphorylation on RR-SRC peptide and EGF-induced receptor autophosphorylation, eitherin vitro or in intact cells was inhibited by hypericin at the same concentration as that in A431 cell proliferation. These data suggest that hypericin directly inhibits EGF-receptor and P56 ^lck PTK activityin vitro and can mediate such actionin vivo.