Neferine induces p38 MAPK/JNK1/2 activation to modulate melanoma proliferation, apoptosis, and oxidative stress

Abstract

Background: Melanoma is a malignant skin cancer that has a poor prognosis in advanced patients. The aim of the present study was to investigate the antitumor role of neferine in melanoma.Methods: A375 and C32 cells were selected as research vectors in vitro. Cell counting Kit-8, 5-ethynyl-2'deoxyuridine staining, transwell, and flow cytometry assay were used to examined cell malignant phenotypes. Mitochondrial dysfunction was detected by 5,50,6,60-tetrachloro-1,10,3,30-tetraethyl-imidacarbocyanine iodide staining and enzyme-linked immunosorbent assay. Reactive oxygen species (ROS) generation was measured using oxidation sensitive fluorescent probe. The phosphorylation activity of p38 and Jun-Nterminal kinase (JNK) 1/2 were examined by Western blot. A xenograft model was established via the subcutaneous injection of A375 cells into the right flank of BALB/c mice in vivo.Results: Neferine (2.5, 5, or 10 μM) treatment inhibited proliferation, invasion, and enhanced apoptotic rate of A375 and C32 cells. Neferine treatment induced abnormal changes in mitochondrial membrane potential. Further studies showed that neferine could significantly increase the production of reactive oxygen species (ROS) and 3,4-methylenedioxyamphetamine (MDA) content, decreased the superoxide dismutase (SOD) level. Neferine (5, 10, or 20 mg/kg) obviously suppressed the weight and size of the xenograft tumor, the number of apoptotic cells in vivo, and the expression of Ki67 + and survivin + decreased. Notably, neferine also activated the phosphorylation of p38 and JNK1/2. Conclusions: Neferine inhibits the proliferative and invasion ability of melanoma cells and promotes their apoptosis, ameliorating the malignant progression of melanoma, likely achieved by upregulating the phosphorylation levels of p38 mitogen-activated protein kinase and JNK1/2.

Myricetin Suppresses Ovarian Cancer In Vitro by Activating the p38/Sapla Signaling Pathway and Suppressing Intracellular Oxidative Stress

“…Oxidative stress affects cell proliferation via various signaling pathways, including EGFR and mTOR pathways that involve key signaling proteins like Ras, Raf, and MAPK pathway factors like ERK1/2, MEK, and p38 ( 25 , 26 ). p38 is a key sensor for oxidative stress, and its redox-sensing function is essential for controlling tumor development ( 27 ).…”

Anti-Allergic and Anti-Inflammatory Effects of Neferine on RBL-2H3 Cells

“…Neferine comes from the lotus core (the embryo of the seed) of the plant Nelumbo nucifera and is a major bisbenzylisoquinoline alkaloid. There is evidence that neferine has a wide range of pharmacological properties, such as anti-cancer, anti-oxidant, antiinflammatory, and neuroprotective effects, in many diseases [10][11][12][13][14][15]. Khan et al found that neferine produces anti-photoaging effects by inhibiting the UV-mediated increase in ROS and malondialdehyde (MDA) levels in human keratinocytes and fibroblasts [16,17].…”

2,5-dimethyl celecoxib induces apoptosis and autophagy via activation of ROS/JNK axis in nasopharyngeal carcinoma cells

“…The JNK, p38, and ERK are mainly included in the MAP-kinase pathway. The pathway is involved in cell proliferation, differentiation, stress adaptation, and apoptosis [ 34 ]. OSU-03012 also suppressed c-Jun NH2-terminal kinase/signal transducers and transcription activators, and MAPK pathways in multiple myeloma cells, according to Zhang and colleagues [ 35 ].…”