Altered mRNA expression related to the apoptotic effect of three xanthones on human melanoma SK-MEL-28 cell line.

Abstract

We previously demonstrated that α-mangostin, γ-mangostin, and 8-deoxygartanin have significant cytotoxic effects on human melanoma SK-MEL-28 cell line. The current study revealed the underlying mechanisms. α-Mangostin (7.5  μg/mL) activated caspase activity, with a 3-fold and 4-fold increased caspase 8 and 9 activity, respectively. The molecular mechanisms were investigated by qRT-PCR for mRNA related to cell cycle arrest in G1 phase (p21(WAF1) and cyclin D1), apoptosis (cytochrome C, Bcl-2, and Bax), and survival pathways (Akt1, NFκB, and IκBα). α-Mangostin significantly upregulated mRNA expression of cytochrome C and p21(WAF1) and downregulated that of cyclin D1, Akt1, and NFκB. γ-Mangostin significantly downregulated mRNA expression of Akt1 and NFκB and upregulated p21(WAF1) and IκBα. 8-Deoxygartanin significantly upregulated the mRNA expression of p21(WAF1) and downregulated that of cyclin D1 and NFκB. The three xanthones significantly inhibited the mRNA expression of the BRAF V600E mutation. Moreover, α-mangostin and γ-mangostin significantly downregulated Akt phosphorylation at Ser473. In conclusion, the three xanthones induced an inhibitory effect on SK-MEL-28 cells by modulating the molecular targets involved in the apoptotic pathways.

• Authors: Jing J Wang, Wei Zhang, Barbara J S Sanderson
• Journal: BioMed research international (Biomed Res Int) Vol. 2013 Pg. 715603 ( 2013) ISSN: 2314-6141 [Electronic] United States
• PMID: 24175297 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCND1 protein, human
• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Protein Kinase Inhibitors
• RNA, Messenger
• RNA, Neoplasm
• Xanthones
• Cyclin D1
• AKT1 protein, human
• Proto-Oncogene Proteins c-akt
• I-kappa B Kinase
• CASP8 protein, human
• CASP9 protein, human
• Caspase 8
• Caspase 9
• mangostin

Topics

• Apoptosis (drug effects)
• Caspase 8 (biosynthesis)
• Caspase 9 (biosynthesis)
• Cell Line, Tumor
• Cyclin D1 (biosynthesis)
• Cyclin-Dependent Kinase Inhibitor p21 (biosynthesis)
• G1 Phase Cell Cycle Checkpoints (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• I-kappa B Kinase (biosynthesis)
• Melanoma (metabolism, pathology)
• Phosphorylation (drug effects)
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-akt (biosynthesis)
• RNA, Messenger (biosynthesis)
• RNA, Neoplasm (biosynthesis)
• Up-Regulation (drug effects)
• Xanthones (pharmacology)