Athyrium multidentatum (Doll.) Ching extract induce apoptosis via mitochondrial dysfunction and oxidative stress in HepG2 cells

Abstract

Athyrium multidentatum (Doll.) Ching (AMC), a unique and nutritious potherb widely distributed in china, has been extensively used in traditional Chinese medicine. Previous studies indicated that AMC extract exhibited antioxidant and antitumor properties. However, the chemical composition of AMC and molecular mechanism of AMC toxicity to HepG2 cells have not yet been elucidated. Hence, this study aimed to investigate the chemical compositions and the underlying mechanisms of the antiproliferative and apoptotic effects of AMC on HepG2. HPLC-MS analysis showed that AMC contain five compounds with chlorogenic acid accounting for 43 percent. Also, AMC strongly inhibited the cell growth and induced apoptosis and cell cycle arrest in HepG2 cells by significantly upregulating the protein expressions of Fas, Fas-L, Bax/Bcl-2, cyto-c, cleaved caspase-3, and PARP in a dose-dependent manner, which indicates AMC induces apoptosis in HepG2 cells through both intrinsic and extrinsic pathways. Moreover, AMC provoked the production of ROS, H2O2, and NO, modulating the PI3K/Akt, MAPK, NFκB and Nrf2 pathways and their downstream transcriptional cascades, ultimately evoked oxidative stress and apoptosis in HpeG2 cells. Further in vivo experiments demonstrated that AMC significantly suppressed the tumor growth, suggesting that AMC may be a novel promising agent for hepatocellular carcinoma treatment.

Oxidative Stress Modulation by Cameroonian Spice Extracts in HepG2 Cells: Involvement of Nrf2 and Improvement of Glucose Uptake

“…The potential involvement of Nrf2, a master regulator of the transcription of genes involved in antioxidation, antioxidant biosynthesis, and metabolic shift, was then highlighted [24]. HepG2 cells showed a relatively high basal level of nuclear Nrf2, in agreement with previous studies [25], which was further increased by H 2 O 2 exposure, but was not affected when the latter was preceded by treatment with either Dichrostachys glomerata or Xylopia parviflora. Interestingly, exposure to Dichrostachys glomerata alone resulted in a reduced Nrf2 accumulation, whereas Xylopia parviflora extract increased Nrf2 translocation, suggesting the involvement of different pathways of antioxidant homeostasis.…”

An In Vitro Estimation of the Cytotoxicity and Genotoxicity of Root Extract from Leonurus sibiricus L. Overexpressing AtPAP1 against Different Cancer Cell Lines

“…Our results indicate that the treatment of K-562, CCRF-CEM and A549 cells with TR and AtPAP1 TR root extracts decreased mitochondrial membrane potential, but better results were observed for the AtPAP1 root extract. Yen et al revealed that Ficus beecheyana root extracts rich in phenolic acids ( p -hydroxybenzoic acid, caffeic acid, chlorogenic acid, p -coumaric acid) may induce apoptosis by decreasing mitochondrial membrane potential in the HL-60 cell line [ 33 ]; however, Qi et al report that Athyrium multidentatum extract, in which the major compound was chlorogenic acid, induces apoptosis via mitochondrial dysfunction in HepG2 cells [ 34 ]. Extracts from L. sibiricus , in which the most dominant compounds were the phenolic acids with chlorogenic acid and caffeic acid, have been found to decrease the mitochondrial membrane potential in glioma cells [ 11 ].…”

Athyrium plants - Review on phytopharmacy properties

“…They have also exhibited a promising effect on the inhibition of cell proliferation and stimulated apoptosis in the human liver cancer cell line (HepG2) 19 . The strong superoxide radical-scavenging and reducing power of Athyrium genus have been attributed to its polysaccharides 19 , 20 …”