Different Apoptotic Effects of Wogonin Via Induction of H2O2 Generation and Ca2+ Overload in Malignant Hepatoma and Normal Hepatic Cells

Wogonin, a major active constituent of Scutellaria baicalensis, possesses potent anticancer activities both in vivo and in vitro. This paper describes the different apoptotic effects of wogonin in HepG2 and L02 cells and the possible mechanism for the differences. Through DAPI staining, Annexin-V/PI double-staining assay, JC-1 detection and the expressions of the key apoptotic proteins, we find that wogonin prefers to induce apoptosis in HepG2 cells through the mitochondrial pathway, while has much less effects on L02 cells. Moreover, overexpression of Bcl-2 can block wogonin-induced apoptosis in HepG2 cells. To illustrate the specific selective mechanism of wogonin in apoptosis induction, H2O2, O-center dot(2)- and Ca2+ are measured by 2',7'-dichlorfluorescein-diacetate, dihydroethidium and Flou-3 AM assay, respectively. The results show that the different apoptotic effects of wogonin in HepG2 and L02 cells are due to the different regulations to the redox balance of reactive oxygen species and the Ca2+ release from endoplasmic reticulum. IP3R-sensitive Ca2+ channels are the key targets of the wogonin-increased H2O2. Besides, the activation of PLC gamma 1 plays as a bridge between H2O2 signal molecules and Ca2+ release. Taken together, wogonin preferentially kills hepatoma cells by H2O2-dependent apoptosis triggered by Ca2+ overload. The results reveal that wogonin is a competitive anticancer drug candidate for the malignant hepatoma therapy. J. Cell. Biochem. 111: 1629-1641, 2010. (C) 2010 Wiley-Liss, Inc.