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Unveiling Therapeutic Opportunities with Melanoma Patient-derived Organoid Models
Published on: September 6, 2024
Proteomics analysis of kojic acid treated A375 human malignant melanoma cells
Jiraporn Nawarak1, Rosa Huang-Liu, Shao-Hsuan Kao
1Institute of Biological Chemistry and Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Abstract:
Although the toxicogenomics of kojic acid treated A375 human malignant melanoma cells has been elucidated, the proteomics of cellular response is still poorly understood. We performed proteomic analysis to investigate the anticancer effect of kojic acid on protein expression profile in A375 cells. A375 cells were treated with kojic acid at 8 microg/mL for 24, 48, and 72 h. With the use of 2-D PAGE and MALDI-Q-TOF MS and MS/MS analyses, proteomic profiles of A375 cells between control and kojic acid treatment were compared, and 30 differentially expressed proteins, containing 2 up-regulated proteins and 28 down-regulated proteins, were identified. Among these proteins, 17 isoforms of 5 identical proteins were observed and 11 chaperone proteins showed the high proportion of protein spots with 36.7% of total proteins. Bioinformatic tools were used to search for protein function and prediction of protein interaction. Sixteen differentially expressed proteins exhibited interaction network linked to the downstream regulations of p53 tumor suppressor and cell apoptosis, which may lead to suppress the melanogenesis and tumorigenesis of kojic acid treated A375 cells. In addition, GRP75, VIME and 2AAA were validated by Western blot analysis, whereas GRP75, 2AAA, HS90B, ENPL and KPYM were validated by RT-PCR. Therefore, these proteins play the important roles in cancer progression and may be potential biomarkers that are useful for diagnostic and therapeutic applications of malignant melanoma cancer.
Insights
Kojic acid alters protein expression in malignant melanoma cells, revealing potential biomarkers for cancer diagnosis and therapy. This study identifies key proteins involved in cell apoptosis and tumor suppression, offering new avenues for melanoma treatment.
Area of Science:
- * Proteomics
- * Cancer Biology
- * Molecular Oncology
Background:
- * The toxicogenomics of kojic acid in A375 human malignant melanoma cells is known, but the proteomic cellular response remains unclear.
- * Understanding protein expression changes is crucial for elucidating anticancer mechanisms.
- * Kojic acid is a potential agent for melanoma treatment, necessitating detailed molecular investigation.
Purpose of the Study:
- * To investigate the anticancer effects of kojic acid on the protein expression profile of A375 human malignant melanoma cells.
- * To identify differentially expressed proteins and their functional roles in response to kojic acid treatment.
- * To explore potential protein biomarkers for malignant melanoma diagnosis and therapy.
Main Methods:
- * Proteomic analysis using 2-D PAGE and MALDI-Q-TOF MS/MS.
- * Comparison of protein expression profiles in A375 cells treated with kojic acid (8 microg/mL) for 24, 48, and 72 hours versus control.
- * Bioinformatic analysis for protein function, interaction networks, and validation by Western blot and RT-PCR.
Main Results:
- * Identified 30 differentially expressed proteins (2 up-regulated, 28 down-regulated) in kojic acid-treated A375 cells.
- * Chaperone proteins constituted a significant portion (36.7%) of the identified protein spots.
- * Sixteen proteins formed an interaction network linked to p53 tumor suppressor and apoptosis pathways, suggesting suppression of melanogenesis and tumorigenesis.
Conclusions:
- * Kojic acid significantly alters the proteome of A375 malignant melanoma cells, impacting key cancer-related pathways.
- * Identified proteins, including GRP75, VIME, 2AAA, HS90B, ENPL, and KPYM, are implicated in cancer progression.
- * These differentially expressed proteins represent potential biomarkers for the diagnosis and therapeutic applications in malignant melanoma.
