L-Mimosine Modulates the ROS/JNK/c-Jun Signaling Axis to Trigger Mitochondrial Apoptosis in Melanoma Cells
10.14148/j.issn.1672-0482.2025.0678
- VernacularTitle:左旋含羞草碱调控ROS/JNK/c-Jun轴诱导黑色素瘤细胞线粒体凋亡的研究
- Author:
Ying ZHAO
1
;
Pan JIANG
1
;
Dan LEI
1
;
Haiyan LIN
1
;
Zhaohai PAN
1
;
Defang LI
1
Author Information
1. 滨州医学院中医学院/烟台市肿瘤代谢中药药理重点实验室/山东省高等学校-中药活性成分生物合成与靶点发现特色实验室,山东 烟台 264003
- Publication Type:Journal Article
- Keywords:
L-mimosine;
melanoma;
A375 cells;
B16 cells;
cell apoptosis;
ROS/JNK/c-Jun
- From:
Journal of Nanjing University of Traditional Chinese Medicine
2025;41(5):678-688
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effects of L-mimosine on the proliferation and apoptosis of melanoma cells and its molecular mechanisms.METHODS The effects of different concentrations of L-mimosine on the viability of melanoma A375 and B16 cells were examined by the MTT assay.The ability of L-Mimosine to affect colony formation was assessed by the plate colony for-mation assay.The effects of L-mimosine on cell apoptosis,reactive oxygen species(ROS),and mitochondrial membrane potential were analyzed by flow cytometry.The changes in the expression levels of intracellular proteins such as Bcl-2,Bax,Cyt C,Cleaved Caspase-3,Cleaved Caspase-9,Bim-EL,Bad,p-JNK,p-c-Jun,p-MKK4,and p-ASK1 were detected by Western blot.The tumor-bearing mouse model was subjected to histological and TUNEL staining analysis of tumor tissues after treatment with normal saline,L-mimosine alone,and L-mimosine in combination with N-acetylcysteine(NAC).RESULTS L-mimosine significantly inhibited the prolifera-tion of A375 and B16 cells and significantly promoted cell apoptosis.Western blot analysis showed that L-mimosine could significantly increase the content of Apaf-1 and Cyt C in the cytoplasm,up-regulate the expression of Cleaved PARP,Cleaved Caspase-3,Cleaved Caspase-9,Bax,Bim-EL and Bad,and down-regulate the expression of anti-apoptotic protein Bcl-2.Further experiments showed that L-mimosine significantly induced the accumulation of ROS in A375 cells and activated the JNK/c-Jun signaling pathway,which was manifested by the significant increase of p-JNK,p-c-Jun,p-MKK4 and p-ASK1.Additionally,the antioxidant NAC could significantly antagonize the ROS accumulation induced by L-mimosine,thereby reversing the pro-apoptotic effects of L-mi-mosine on melanoma cells.In vivo experiments,NAC also significantly antagonized the tumor growth inhibition induced by L-mi-mosine,as evidenced by increased tumor volume and reversed expression levels of apoptosis-related proteins.CONCLUSION L-mi-mosine induces apoptosis in melanoma cells by increasing ROS levels and activating the JNK/c-Jun signaling pathway.
