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Scutellarin regulates MAPK/ERK signalling in nasopharyngeal cancer via the apoptotic and ROS induced DNA damage
Jingda Xu1, Guanzheng Wu2, Lu Wang3
1Faculty of Chinese Medicine, Macau University of Science and Technology, Macau 999078, China; Department of Otolaryngology, Zhuhai Hospital of Integrated Traditional Chinese and Western Medicine, Zhuhai Guangdong, 519000, China.
Abstract:
Nasopharyngeal carcinoma (NPC) occurs frequently, and NPC poses a significant risk to public health in areas where it is endemic. Better care is needed because NPC is associated with considerable morbidity and mortality. A natural anticancer substance called scutellarin fights cancer by acting on a variety of signalling pathways. Nevertheless, little is known about the underlying apoptotic and anti-proliferative actions of scutellarin. The current study aimed to determine the molecular effects of in vitro scutellarin on CNE1 human NPC cells through mechanisms such as cell proliferation, anti-inflammatory, and anti-apoptotic effects. NPC cells were exposed to scutellarin (20 and 30 μM/ml), and their proliferation and apoptosis were evaluated using the MTT assay, AO/EB, Rh-123, DCFH-DA, DAPI, and PI staining, cell adhesion, cell migration, and western blot analysis. We evaluated putative molecular pathways, MAPKs/NF-κB signaling, MMP, and intracellular ROS, cell proliferation regulatory proteins. By generating intracellular ROS, causing MMP loss and inducing apoptosis via the signalling pathways of TNF-α, COX-2, iNOS, and IL-6, pRB, cyclin-D1, CDK4/CDK6, and MAPKs/NF-κB, it has been found that scutellarin may reduce the proliferative, inflammatory, migratory, and invasive capacity of NPC cells. Our research supports the MAPKs/NF-κB pathway as a therapeutic target and suggests that it may play a key role in mediating the scutellarin actions against nasopharyngeal cancer malignancy. In summary, scutellarin may be an effective conventional therapeutic drug in preventing the progression of NPC.
Insights
Scutellarin, a natural compound, effectively inhibits nasopharyngeal carcinoma (NPC) cell growth and spread. It works by inducing cell death and reducing inflammation through the MAPKs/NF-κB signaling pathway.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Nasopharyngeal carcinoma (NPC) is a significant public health concern in endemic regions, associated with high morbidity and mortality.
- Existing treatments for NPC require improvement due to associated complications.
- Scutellarin, a natural compound, exhibits anticancer properties, but its specific mechanisms in NPC are not fully understood.
Purpose of the Study:
- To investigate the in vitro molecular mechanisms of scutellarin's anti-cancer effects on CNE1 human NPC cells.
- To evaluate scutellarin's impact on NPC cell proliferation, apoptosis, and inflammatory responses.
- To elucidate the role of signaling pathways, including MAPKs/NF-κB, in mediating scutellarin's action.
Main Methods:
- CNE1 human NPC cells were treated with scutellarin (20 and 30 μM/ml).
- Assays included MTT, AO/EB, Rh-123, DCFH-DA, DAPI, and PI staining to assess proliferation, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS).
- Western blot analysis was used to evaluate key proteins and signaling pathways (MAPKs/NF-κB, TNF-α, COX-2, iNOS, IL-6, pRB, cyclin-D1, CDK4/CDK6).
Main Results:
- Scutellarin significantly reduced NPC cell proliferation, migration, and invasion.
- The compound induced apoptosis by generating intracellular ROS and causing MMP loss.
- Scutellarin modulated the MAPKs/NF-κB signaling pathway, along with key inflammatory mediators and cell cycle regulatory proteins.
Conclusions:
- Scutellarin demonstrates potent anti-proliferative, anti-inflammatory, and pro-apoptotic effects against NPC cells in vitro.
- The MAPKs/NF-κB signaling pathway is a key mediator of scutellarin's anti-cancer activity in NPC.
- Scutellarin holds promise as a potential therapeutic agent for nasopharyngeal carcinoma.
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