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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Genistein and Curcumin Inhibit Proliferation and Invasiveness in BRAFV600E Mutant and Wild-Type Melanoma Cells:
Federico Vaccaro1, Federica Mannino2, Mariacarmela Santarpia3
1Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, Via C. Valeria, 98125 Messina, Italy.
Abstract:
Background/objectives: Melanoma is one of the deadliest forms of malignant cancers; ultraviolet radiation exposure together with genetic mutations, such as BRAF, represent the main risk factors and are involved in metastatic dissemination. Previous studies demonstrated the anti-emetic and anti-proliferative effects of the flavonoid genistein and the turmeric curcumin in cancers. This study aimed at investigating the anticancer effects of curcumin, genistein and their association in melanoma cells. Methods: Human A375 and CHL-1 cell lines were cultured and treated with different concentrations of curcumin or genistein or curcumin + genistein for 24 h according to IC50. Results: Genistein and curcumin induced cell death, as demonstrated by MTT assay and FDA/PI staining. The anti-apoptotic protein Bcl-2 was significantly reduced after curcumin and curcumin + genistein treatment, but unexpectedly not with genistein alone. Curcumin and genistein significantly increased DNA fragmentation, thus indicating apoptosis induction. Moreover, comet assay confirmed that curcumin and genistein stimulated cell death, as quantified by measuring the displacement between the 'comet head' and the resulting 'tail'. FAK protein expression was significantly reduced by genistein and curcumin in CHL-1 cells and after the treatment with genistein + curcumin in the most aggressive A375 cells. These anti-proliferative effects were confirmed by scratch assay and phospho-p38 reduction. Moreover, both curcumin and genistein alone and in association inhibited cell adhesion, thus indicating that these nutraceuticals could reduce invasion and metastasis. Conclusion: The obtained results provided new insights for the anticancer effects of genistein and curcumin, which could be used to improve therapeutic adherence and drug response.
Insights
Curcumin and genistein, natural compounds found in turmeric and soy, effectively induce melanoma cell death and inhibit cancer spread. These findings suggest potential therapeutic benefits for melanoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Melanoma is a deadly cancer with UV radiation and BRAF mutations as key risk factors.
- Genistein (a flavonoid) and curcumin (from turmeric) show known anti-cancer properties.
- Investigating their combined effects on melanoma is crucial for new therapeutic strategies.
Purpose of the Study:
- To evaluate the individual and combined anticancer effects of curcumin and genistein in human melanoma cell lines.
- To explore the molecular mechanisms underlying their anti-proliferative and pro-apoptotic actions.
Main Methods:
- Human melanoma cell lines (A375, CHL-1) were treated with varying concentrations of curcumin and genistein.
- Cell viability (MTT assay), apoptosis (FDA/PI staining, DNA fragmentation, comet assay), protein expression (Bcl-2, FAK, phospho-p38), and cell adhesion were assessed.
Main Results:
- Both curcumin and genistein induced significant melanoma cell death and apoptosis.
- Combined treatment reduced Bcl-2 expression, while both compounds increased DNA fragmentation.
- FAK and phospho-p38 expression were reduced, and cell adhesion was inhibited, suggesting reduced invasion and metastasis.
Conclusions:
- Curcumin and genistein exhibit potent anticancer effects against melanoma cells, individually and in combination.
- These nutraceuticals demonstrate potential in reducing melanoma cell proliferation, inducing apoptosis, and inhibiting metastasis.
- Findings support the use of genistein and curcumin to enhance therapeutic adherence and drug response in melanoma treatment.
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