Different apoptotic effects of wogonin via induction of H(2)O(2) generation and Ca(2+) 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, H(2)O(2), (·)O(2)(-) and Ca(2+) 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 Ca(2+) release from endoplasmic reticulum. IP(3)R-sensitive Ca(2+) channels are the key targets of the wogonin-increased H(2)O(2). Besides, the activation of PLCγ1 plays as a bridge between H(2)O(2) signal molecules and Ca(2+) release. Taken together, wogonin preferentially kills hepatoma cells by H(2)O(2)-dependent apoptosis triggered by Ca(2+) overload. The results reveal that wogonin is a competitive anticancer drug candidate for the malignant hepatoma therapy.
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, The People's Republic of China.
Libin
L
Wei
Na
N
Lu
Qinsheng
Q
Dai
Jingjing
J
Rong
Yan
Y
Chen
Zhiyu
Z
Li
Qidong
Q
You
Qinglong
Q
Guo
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
D044950:Flavanones; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; C085514:wogonin; D002118:Calcium