Induction of apoptosis and G1 phase cell cycle arrest by Aster�incises in AGS gastric adenocarcinoma cells

Abstract

In recent decades, various bioactive compounds from plants have been investigated for their potential use in the treatment of diseases in humans. Aster incisus extract (AIE) is the extract of a common plant that is mostly found in Asia. It has traditionally been used for medicinal purposes in South Korea. In this study, we evaluated the potential anticancer effects of a methanolic extract of Aster incisus in a normal human cell line (HaCaT keratinocytes) and in 4 different types of human cancer cell lines (A549, lung cancer; Hep3B, liver cancer; MDA‑MB‑231, breast cancer; and AGS, gastric cancer). The HaCaT, A549, Hep3B, MDA‑MB‑231 and AGS cells were treated with various concentrations of AIE and following treatment, cell survival was evaluated. Additional analyses, such as WST-1 assay, western blot analysis, DAPI staining, flow cytometry, immunofluorescence staining and wound healing assay were performed to elucidate the mechanisms and pathways involved in the cell death induced by AIE. Treatment with AIE induced morphological changes and considerably reduced the viability of the both normal and cancer cell lines. Further analysis of the AGS gastric cancer cells revealed that AIE led to the induction of apoptosis and a high accumulation of cells in the G1 cell phase following treatment with AIE in a dose-dependent manner. The results also revealed that AIE successfully suppressed the migration of the AIE-treated AGS cells. The results of western blot analysis indicated that AIE increased the expression of pro-apoptotic proteins, particularly Bid, Bad, Bak, cytochrome c, apoptosis inducing factor (AIF), cleaved caspase‑3, -8 and -9 and cleaved poly(ADP-ribose) polymerase (PARP). Additionally, AIE decreased the expression of the anti-apoptotic proteins, Bcl-2 and Bcl-xL. On the whole, the findings of this study demonstrate that AIE induces apoptosis through the activation of the caspase‑dependent pathway mediated by the mitochondrial pathway and by arresting the cell cycle in AGS cells.

Effects of 2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone from Syzygium nervosum Seeds on Antiproliferative, DNA Damage, Cell Cycle Arrest, and Apoptosis in Human Cervical Cancer Cell Lines

“…After treatment with DMC, HeLa cells showed increasing DNA damage, G 0 /G 1 phases, and induced apoptosis cell death when compared to the untreated and 1% DMSO groups. These results suggest that the cell death mechanism by the ATM and ATR signalling pathways after increased DNA damage activates the p53 protein through the CHK1 and CHK2 regulator proteins, leading to cell cycle arrest and induced apoptosis cell death [41][42][43]. Accordingly, the findings of the current study suggest an antiproliferative cervical cancer effect of DMC through the induction of the cell death mechanism.…”

Astaxanthin induces NADPH oxidase activation and receptor‑interacting protein kinase 1‑mediated necroptosis in gastric cancer AGS cells

“…It is important to characterize human tumor cells in vitro in a detailed manner, as they serve as useful model systems for studies involving heterogeneous responses to anticancer drugs (57). Recently, this cell line has been widely used as a model system for evaluating cancer cell apoptosis (58)(59)(60).…”

“…AGS cells have more genetic changes and higher growth rates than normal cells (60,61). One example is tripartite motif containing 25 (TRIM25), a member of TRIM proteins that has been implicated in carcinogenesis.…”

Emerging Potential of Naturally Occurring Molecules against Gastric Cancer: Insights Molecular Mechanism and Therapeutic Targets

“…The studies performed cell cycle analysis through flow cytometry to observe cell cycle distribution, albeit the proteins responsible for the event were not confirmed in a large portion of the investigations. Berberine, TTF, ginsenoside-Rh2, crosolic acid, rottlerin, grifolin, methanol extract of aster incises (Asteraceae), organic extract of Amorphophallus konjac K.Koch Tuber (Araceae), and xiao tan he wei decoction induced G0/G1 phase cell cycle arrest [38,45,49,58,62,87,90,105,109]. Toosendanin increased the proportion of cells in the G1 and S phase [67,68].…”