Antitumor activity and expression profiles of genes induced by sulforaphane in human melanoma cells
| Autor: | Alessandra Pistilli, Mario Rende, Stefano Calvieri, Ugo Bottoni, Andrea Crisanti, Ekaterina Kuligina, Paola Arcidiacono, Francesco Ragonese, Anna Maria Stabile, Roberta Spaccapelo |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
NF-KAPPA-B Medicine (miscellaneous) Apoptosis medicine.disease_cause chemistry.chemical_compound 0302 clinical medicine Isothiocyanates RNA-Seq TRANSCRIPTION FACTOR Melanoma INDUCED APOPTOSIS Nutrition and Dietetics PROSTATE-CANCER CELLS Original Contribution Gene Expression Regulation Neoplastic ISOTHIOCYANATE SULFORAPHANE 030220 oncology & carcinogenesis Sulfoxides Melanocytes GADD45B Life Sciences & Biomedicine Programmed cell death Sulforaphane Transcriptome BREAST-CANCER DNA-DAMAGE PHENETHYL ISOTHIOCYANATE MESENCHYMAL TRANSITION PROMISING MOLECULE Cell Survival Biology 03 medical and health sciences Cell Line Tumor medicine Anticarcinogenic Agents Humans Viability assay Protein kinase B Science & Technology Nutrition & Dietetics medicine.disease Molecular biology 030104 developmental biology chemistry Brassicaceae Cancer research 1111 Nutrition And Dietetics Carcinogenesis Thiocyanates |
| Zdroj: | European Journal of Nutrition |
| Popis: | Purpose Human melanoma is a highly aggressive incurable cancer due to intrinsic cellular resistance to apoptosis, reprogramming, proliferation and survival during tumour progression. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, plays a role in carcinogenesis in many cancer types. However, the cytotoxic molecular mechanisms and gene expression profiles promoted by SFN in human melanoma remain unknown. Methods Three different cell lines were used: two human melanoma A375 and 501MEL and human epidermal melanocytes (HEMa). Cell viability and proliferation, cell cycle analysis, cell migration and invasion and protein expression and phosphorylation status of Akt and p53 upon SFN treatment were determined. RNA-seq of A375 was performed at different time points after SFN treatment. Results We demonstrated that SFN strongly decreased cell viability and proliferation, induced G2/M cell cycle arrest, promoted apoptosis through the activation of caspases 3, 8, 9 and hampered migration and invasion abilities in the melanoma cell lines. Remarkably, HEMa cells were not affected by SFN treatment. Transcriptomic analysis revealed regulation of genes involved in response to stress, apoptosis/cell death and metabolic processes. SFN upregulated the expression of pro-apoptotic genes, such as p53, BAX, PUMA, FAS and MDM2; promoted cell cycle inhibition and growth arrest by upregulating EGR1, GADD45B, ATF3 and CDKN1A; and simultaneously acted as a potent inhibitor of genotoxicity by launching the stress-inducible protein network (HMOX1, HSPA1A, HSPA6, SOD1). Conclusion Overall, the data show that SFN cytotoxicity in melanoma derives from complex and concurrent mechanisms during carcinogenesis, which makes it a promising cancer prevention agent. Electronic supplementary material The online version of this article (doi:10.1007/s00394-017-1527-7) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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