Ampelopsin‑induced reactive oxygen species enhance the apoptosis of colon cancer cells by activating endoplasmic reticulum stress‑mediated AMPK/MAPK/XAF1 signaling

Abstract

Abstract. Ampelopsin (Amp) is bioactive natural product and exerts anti-cancer effects against several cancer types. The present study investigated the anti-colon cancer activity of Amp and explored its mechanism of action. The treatment of colon cancer cells with Amp resulted in the dose-and time-dependent induction of apoptosis via the activation of endoplasmic reticulum (ER) stress, 5' adenosine monophosphate-activated protein kinase (AMPK), and c-Jun N-terminal protein kinase (JNK)/p38 mitogen-activated protein kinases (MAPKs). Salubrinal, an ER stress inhibitor, prevented the upregulation of ER stress-associated proteins, including phosphorylated protein kinase RNA-like ER kinase, phosphorylated eukaryotic translation initiation factor 2α, glucose-regulated protein 78, and CCAAT/enhancer-binding protein homologous protein, as well as suppressing AMPK activation and the MAPK signaling pathway. Knockdown of AMPK by RNA interference failed to block ER stress. Additionally, SP600125 (a JNK inhibitor) and SB203580 (a p38-MAPK inhibitor) effectively inhibited apoptosis and attenuated the expression of X-linked IAP-associated factor 1 (XAF1) and apoptotic Bcl-2 family proteins (BCL2 antagonist/killer 1 and BCL2-associated X protein) in Amp-treated colon cancer cells. Furthermore, reactive oxygen species (ROS)-mediated ER stress/AMPK apoptotic signaling pathway in Amp-treated colon cancer cells were markedly inhibited by treatment with N-acetyl-L-cysteine, a ROS scavenger. These results demonstrate that treatment with Amp induces the apoptotic death of colon cancer cells through ER stress-initiated AMPK/MAPK/XAF1 signaling. These results also provide experimental information for developing Amp as therapeutic drug against colon cancer.

Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells

“…The relationships among ER stress, autophagy and ROS are rather complicated. Several studies showed that ER stress and autophagy were stimulated by the production of ROS 43 , 44 . However, the increasing number of studies has illustrated that ER stress and autophagy could disrupt the delicate balance between ROS production and degradation 45 , 46 .…”

Regulation of signaling pathways by Ampelopsin (Dihydromyricetin) in different cancers: exploring the highways and byways less travelled

“…Salubrinal pretreatment effectively attenuated Ampelopsin-induced phosphorylation of p38-MAPK and JNK (42). Additionally, ER stress inhibition markedly reduced the Ampelopsindependent phosphorylation of AMPK and expression of XAF1 (XIAP-Associated Factor-1) in colon cancer cells (42). Overall these findings clearly showcased that Ampelopsin induced apoptotic death in colon cancer cells through ER stress-driven AMPK/MAPK/XAF1 signaling axis.…”

“…Ampelopsin induced an increase in phosphorylated levels of p38-MAPK and JNK. Salubrinal pretreatment effectively attenuated Ampelopsin-induced phosphorylation of p38-MAPK and JNK (42). Additionally, ER stress inhibition markedly reduced the Ampelopsindependent phosphorylation of AMPK and expression of XAF1 (XIAP-Associated Factor-1) in colon cancer cells (42).…”

Analysis of Low Cancer Mortality Rates in the Wine Regions of Tokaj and Balaton in Hungary

“…The highly elevated pro-oxidant capability of Botrytis wines was firstly observed and described by Sipka and coworkers [16]; in addition, the anti-oxidant capacity of Aszú wines was found to be much less than that of red wines (not published observation, Sipka, 2019). (b) The remarkably higher amounts of iron (Fe 2+ 6-18 mg/L) occurring in all these wines compared to those in red wines (2.0-3.0 mg/L) [3] could react with H 2 O 2 (e.g., in the Fenton reaction) and could induce an increased production of reactive oxygen species (ROS) leading to apoptosis in colon cancer cells [17]. Additionally, H 2 O 2 could stimulate the natural killer cells attacking the tumor cells [18].…”