Different apoptotic effects of wogonin via induction of H₂O₂ generation and Ca²⁺ overload in malignant hepatoma and normal hepatic cells

Abstract

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.

Single-walled carbon nanohorn (SWNH) aggregates inhibited proliferation of human liver cell lines and promoted apoptosis, especially for hepatoma cell lines

“…33,34 As a type of critical target cell line for the study of liver cancer therapy, HepG2 has been investigated by many researchers. 35,36 How SWNHs affect the biological functions of human hepatoma cell lines such as HepG2 or normal liver cell lines such as L02 was unknown, and there were no reports on the differences in roles and mechanisms between the material and the normal or cancer cells. To address these…”

Periodic Mechanical Stress INDUCES Chondrocyte Proliferation and Matrix Synthesis via CaMKII-Mediated Pyk2 Signaling

“…Accumulated evidence has shown that CaMKII activation is closely related to increased intracellular calcium levels [8, 9]. In addition, PLCγ1 signaling has also been proven to facilitate the influx of intracellular Ca 2+ [14, 15]. Thus, PLCγ1 may be located upstream of CaMKII by influencing intracellular calcium levels in some cases.…”

“…In our previous study, we demonstrated that PLCγ1, known as an important serine threonine kinase of PLC, is activated in response to periodic mechanical stress [13]. Increasing evidence suggests that PLCγ1 activation elevates the levels of cytosolic Ca 2+ by increasing calcium release from the endoplasmic reticulum [14, 15]. Thus, we have reason to speculate that in chondrocytes, periodic mechanical stress-induced PLCγ1 activation would induce the influx of intracellular Ca 2+ that is responsible for the activation of CaMKII.…”

III-10, a newly synthesized flavonoid, induces cell apoptosis with the involvement of reactive oxygen species-mitochondria pathway in human hepatocellular carcinoma cells

“…A number of flavonoids were shown to have both pro-and antioxidant effects on cancer cells, by ϭϳ their ability to deplete glutathione (GSH) of tumor cells (Li-Weber, 2009). Moreover, wogonin was shown to deoxidize .O-to H 2 O 2 via the antiradical enzyme SOD, shifting the redox balance of reactive oxygen species to a more reductive state and heightened the total reactive oxygen species levels (Wei et al, 2010). Therefore it is believed that the anticancer activity of flavonoids may also involve a pro-oxidant mechanism.…”