Lappaconitine hydrochloride induces apoptosis and S phase cell cycle arrest through MAPK signaling pathway in human liver cancer HepG2 cells

Background: Lappaconitine (LA), isolated from the root of Aconitum sinomontanum Nakai, had definite pharmacological effects, such as anticancer, analgesia, and anti-inflammation. LA and its derivatives had garnered prevalent consideration due to its analgesic and antitumor effects, but its clinical application was constrained by poor solubility. In this study, a novel LA hydrochloride (LH) was synthesized to upsurge the solubility and improve the efficacy. Objectives: The objective of this study was to examine the antitumor effect and primary mechanisms of LH on cell proliferation, cell cycle, and apoptosis in HepG2 cells. Materials and Methods: The cell viability and proliferation were assessed using Cell Counting Kit-8 and 5'-ethynyl-2'-deoxyuridine assay. The apoptosis morphological feature of cell was detected with the 4',6-diamidino-2-phenylindole (DAPI) staining method. The effect of protein expression levels was recognized by Western blot assay. Cell cycle and apoptosis were estimated using flow cytometer. Results: LH repressed cell viability and proliferation of HepG2 cells and persuaded apoptosis in a dose-dependent way. Flow cytometry analysis results display that LH could arrest cell cycle of HepG2 cells in S phase, thereby preventing cells entering G2/M phase. LH upregulated the expression of cytochrome C, Bax, P53, cleaved caspase-3, cleaved caspase-9, and cleaved poly ADP-ribose polymerase (PARP) and suppressed the expression of Bcl-2. Furthermore, caspase inhibitor z-VAD-fmk inhibited the activation of cleaved caspase-3 and cleaved caspase-9. Moreover, LH abridged the phosphorylation levels of extracellular signal-regulated kinase and augmented the phosphorylation levels of c-Jun N-terminal kinase and P38. Conclusion: LH designated antitumor effect against HepG2 cells through suppressing cell proliferation, inducing apoptosis and cell cycle arrest by aiming mitogen-activated protein kinase signaling pathway.