title: 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.affiliation: Department of Medical Biotechnology, Flinders Medical Sciences and Technology, School of Medicine, Faculty of Health Science, Flinders University, Level 4, Health Science Building, Registry Road, Bedford Park, Adelaide, SA 5042, Australia ; Flinders Centre for Marine Bioproducts Development (FCMBD), Flinders University, Level 4, Health Science Building, Registry Road, Bedford Park, Adelaide, SA 5042, Australia.
authors.forename: Jing J
authors.initials: JJ
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Barbara J S
authors.initials: BJ
authors.lastname: Sanderson
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053181:Caspase 8 / Q000096:biosynthesis; D053453:Caspase 9 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051550:I-kappa B Kinase / Q000096:biosynthesis; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects; D044004:Xanthones / Q000494:pharmacology*
chemical_list: C530104:CCND1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D044004:Xanthones; D019938:Cyclin D1; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; C021053:mangostin