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Updated: Jan 8, 2026
Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Serine/Arginine Protein Kinase Inhibitors Potentiate Melanoma Cell Death and Metastatic Inhibition Through Apoptotic
Atit Silsirivanit1, Chaturong Inpad2, Jesadagorn Siriwath3
1Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
Purpose:
Melanoma arises from the malignant transformation of melanocytes, a serious health problem in high UV-exposure countries. Ineffective treatments and metastasis have led to poor prognosis and high mortality among melanoma patients. Several underlying mechanisms are suspected. The splicing-error in many genes has been frequently reported in melanoma, therefore, targeting splicing regulator Serine/Arginine protein kinases (SRPKs) is promising.
Methods:
SRPKs expression in the TCGA dataset was analyzed by GEPIA. A375 and MNT-1 were comparatively treated by SRPK inhibitors, SRPIN340 and SPHINX31. Effects on viability and growth were measured by MTT and hanging drop assay. Apoptotic death was examined by flow cytometry and western blotting. Invasive ability was determined by transwell assay. Invasive-associated genes, proteins, and enzymes were tracked by RT-PCR, western blotting, immunofluorescence, and gelatin zymography.
Results:
SRPIN340 exhibited higher inhibitory effects on the viability and growth of melanoma cells than SPHINX31. Apoptotic induction was found with downregulated Bcl-2 and upregulated cytochrome c, especially in A375 cells. For metastatic inhibition in A375, lower numbers of invaded cells were counted. Downregulated vimentin mRNA and transcription factors-snail, as well as altered vimentin protein expression and localization were marked. Remarkably, the activities of MMP2 and MMP9 were suppressed.
Conclusion:
SRPK inhibitors potentially suppressed melanoma cell survivability and metastasis through the triggering of apoptotic proteins and dysregulating vimentin. These collected data serve as a basis for utilizing new alternative therapeutic strategies by targeting splicing regulator SRPK, for melanoma treatment.
Insights
Targeting Serine/Arginine protein kinases (SRPKs) with inhibitors like SRPIN340 shows promise for melanoma treatment. These SRPK inhibitors reduced melanoma cell viability, growth, and metastasis by inducing apoptosis and altering vimentin expression.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Melanoma, a significant health concern in high UV-exposure regions, is characterized by high mortality due to ineffective treatments and metastasis.
- Splicing errors in genes are frequently observed in melanoma, suggesting that targeting splicing regulators like Serine/Arginine protein kinases (SRPKs) could be a viable therapeutic strategy.
Purpose of the Study:
- To investigate the therapeutic potential of SRPK inhibitors in melanoma.
- To evaluate the effects of SRPK inhibitors on melanoma cell viability, growth, apoptosis, and metastasis.
Main Methods:
- Analysis of SRPKs expression using TCGA dataset and GEPIA.
- Comparative treatment of melanoma cell lines (A375, MNT-1) with SRPK inhibitors (SRPIN340, SPHINX31).
- Assessment of cell viability, growth, apoptosis, and invasion using MTT assays, hanging drop assays, flow cytometry, western blotting, transwell assays, RT-PCR, immunofluorescence, and gelatin zymography.
Main Results:
- SRPIN340 demonstrated superior inhibitory effects on melanoma cell viability and growth compared to SPHINX31.
- SRPK inhibition induced apoptosis, evidenced by downregulated Bcl-2 and upregulated cytochrome c, particularly in A375 cells.
- Inhibition of melanoma cell invasion was observed, with downregulated vimentin mRNA and snail transcription factor, and suppressed MMP2 and MMP9 activities.
Conclusions:
- SRPK inhibitors show potential in suppressing melanoma cell survivability and metastasis.
- Targeting SRPKs may offer a novel therapeutic approach for melanoma treatment by modulating apoptosis and vimentin-related pathways.
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