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Neferine induces apoptosis by modulating the ROS‑mediated JNK pathway in esophageal squamous cell carcinoma
Kang An1, Yuehan Zhang1, Yingjiao Liu1
1Department of Gastroenterology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.
Abstract:
Current treatments for esophageal squamous cell carcinoma (ESCC) have limited efficacy. Therefore, the development of novel therapeutic targets to effectively manage the disease and boost survival rates is imperative Neferine, a natural product extracted from Nelumbo nucifera (lotus) leaves, has been revealed to inhibit the growth of hepatocarcinoma, breast cancer and lung cancer cells. However, its effect on ESCC is unknown. In the present study, it was revealed that neferine exerted anti‑proliferative effects in ESCC. It was also revealed that it triggered arrest of the G2/M phase and enhanced apoptosis of ESCC cell lines. Moreover, its ability to trigger accumulation of reactive oxygen species (ROS) and activate the c‑Jun N‑terminal kinase (JNK) pathway was demonstrated. Further study revealed how N‑acetyl cysteine (NAC), a ROS inhibitor, attenuated these effects, demonstrating that ROS and JNK inhibitors mediated a marked reversal of neferine‑triggered cell cycle arrest and apoptosis in ESCC cells. Finally, it was revealed that neferine was involved in the inhibition of Nrf2, an antioxidant factor. Collectively, these findings demonstrated the antitumor effect of neferine in ESCC, through the ROS‑mediated JNK pathway and inhibition of Nrf2, indicating its potential as a target for development of novel and effective therapeutic agents against ESCC.
Insights
Neferine, a natural compound, shows promise in treating esophageal squamous cell carcinoma (ESCC). It inhibits cancer cell growth by activating the ROS-JNK pathway and inhibiting Nrf2.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Esophageal squamous cell carcinoma (ESCC) treatments have limited efficacy.
- Novel therapeutic targets are crucial for improving patient survival rates.
- Neferine, a natural product from Nelumbo nucifera, inhibits various cancer cells but its effect on ESCC is unknown.
Purpose of the Study:
- To investigate the anti-cancer effects of neferine on ESCC.
- To elucidate the underlying molecular mechanisms of neferine's action in ESCC.
Main Methods:
- Assessing neferine's anti-proliferative effects on ESCC cell lines.
- Analyzing cell cycle progression (G2/M arrest) and apoptosis induction.
- Measuring reactive oxygen species (ROS) generation and JNK pathway activation.
- Investigating the role of N-acetyl cysteine (NAC) as a ROS inhibitor.
- Examining the impact of neferine on Nrf2 expression.
Main Results:
- Neferine demonstrated significant anti-proliferative effects on ESCC cells.
- Neferine induced G2/M phase arrest and enhanced apoptosis.
- Neferine triggered ROS accumulation and activated the JNK pathway.
- ROS and JNK inhibition reversed neferine-induced cell cycle arrest and apoptosis.
- Neferine inhibited the antioxidant factor Nrf2.
Conclusions:
- Neferine exhibits antitumor effects against ESCC.
- The mechanism involves ROS-mediated JNK pathway activation and Nrf2 inhibition.
- Neferine shows potential as a novel therapeutic agent for ESCC.
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