Anti-tumor Properties of <i>Picrasma quassioides</i> Extracts in H-Ras<sup>G12V</sup> Liver Cancer Are Mediated Through ROS-dependent Mitochondrial Dysfunction
DAN-PING XIE, Yi-Xi Gong, Yinghua Jin, Chenxi Ren, Yue Liu, Ying‐Hao Han, Meihua Jin, Dan Zhu, Pan Qiu-zhen, Liyun Yu, Dong‐Seok Lee, Jaihyung Lee, Ji-Hwan Kim, Yang Ho Park, Jin Won Hyun, Taeho Kwon, Yudong Cui, Hu‐Nan Sun
Abstract
Background: Picrasma quassioides (PQ) is a traditional Asian herbal medicine with anti-tumor properties that can inhibit the viability of HepG2 liver cancer cells. H-Ras is often mutated in liver cancer, however, the effect of PQ treatment on H-Ras mutated liver cancer is unclear. This study aimed to investigate the role of PQ on ROS accumulation and mitochondrial dysfunction in H-ras mutated HepG2 (HepG2<sup>G12V</sup>) cells. Materials and Methods: PQ ethanol extract-induced HepG2<sup>G12V</sup> apoptosis was analyzed by the MTT assay, fluorescence microscopy, flow cytometry and western blotting. Results: PQ treatment affected cell migration and colony formation in HepG2<sup>G12V</sup> cells. Cleaved-caspase-3, cleaved-caspase-9 and BCL2 associated agonist of cell death (BAD) expression levels were increased, while the levels of B-cell lymphoma-extra large (Bcl-xL) were decreased with PQ treatment. PQ treatment led to a reduction of H-Ras expression levels in liver cancer cells, thus reducing their abnormal proliferation. Furthermore, it led to increased expression levels of Peroxiredoxin VI, which regulates the redox signal in cells. Conclusion: Taken together these results provide a new functional significance for the role of PQ in treating HepG2<sup>G12V</sup> liver cancer.