NF-κB, JNK and p53 pathways are involved in tubeimoside-1-induced apoptosis in HepG2 cells with oxidative stress and G₂/M cell cycle arrest

Tubeimoside-1 is a triterpenoid saponin extracted from the traditional Chinese herb Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae). We investigated the cytotoxic effect and apoptosis mechanism of tubeimoside-1. Tubeimoside-1 was cytotoxic in seven human cancer cell lines, with HepG2 the most sensitive. Tubeimoside-1 induced apoptosis of HepG2 cells dose and time dependently. Both the extrinsic and intrinsic pathways were triggered by tubeimoside-1. Caspase-3, -8 and -9 were activated and the expression of Fas, Fas ligand, Bcl-2, Bak and Bax was regulated. Moreover, tubeimoside-1 induced accumulation of reactive oxygen species and arrested cell cycle at the G(2)/M phase, thus contributing to apoptosis, through signaling regulation by tumor necrosis factor α, nuclear factor κB (NF-κB), Jun N-terminal kinase (JNK) and p53. We provide further insight into the tubeimoside-1 cytotoxic effect for antitumor chemotherapeutic treatment.