Nonselective Cell Necrosis Mediated by the Total Flavones of Penthorum Chinensis Pursh and Thonningianin-A in Human Hepatic and Hepatoma Cells

Abstract

Penthorum chinensis Pursh (PCP), family Penthoraceae, has been used for hundreds of years in China. With the launch of PCP tablets, clinical applications focused on liver fibrosis and hepatocarcinoma. The purpose of this research was to explore the selectivity and toxicity of the active pharmacodynamic ingredients of PCP in vitro. The total flavones of PCP (TFPCE) and thonningianin-A (Th-A), a major flavone in TFPCE, were investigated on the cell death patterns in human hepatoma cells (HepG2) and human hepatic cells (LO2), followed by a concentration detection of LDH in the supernatants. Apoptosis and necrosis detection kits were used to validate the patterns of cell death caused by TFPCE and Th-A. Finally, the cytotoxicity of both TFPCE and Th-A were reproduced in the colorectal adenocarcinoma cells (NCI-H716). The results indicated that TFPCE inhibits the cell viability of HepG2 cells at a concentration lower than 25 μg/mL. Alternatively, the cell viability of LO2 cells dramatically decreased in the treatment of TFPCE at 25 μg/mL. The effects of Th-A on the cell viability of HepG2 cells and LO2 cells were consistent with TFPCE. LDH detection indicated that TFPCE and Th-A increased the LDH concentration of the supernatants in a dose-dependent way, indicating the pattern of cell necrosis. Fluorescence staining verified the necrosis cell death caused by TFPCE and Th-A. A dose-dependent tendency was obtained in NCI-H716 cells, indicating that the cell viability of NCI-H716 cells was significantly suppressed with the treatment of TFPCE and Th-A. Our results bring the potential toxicity of PCP to the forefront of public attention. Therefore, the clinical application of P chinensis is required to focus more on its cytotoxic effect.