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

Wang JJ, Zhang W, Sanderson BJ - Biomed Res Int (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

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Caspase 8 (a) and 9 (b) activities were determined using luminescent kits as described in the method for SK-MEL-28 cell line treated with xanthones for 48 h. The values are shown as the mean ± SEM (n = 3). Treatments significantly different from the untreated control at P < 0.05 are presented as ∗ and at P < 0.01 as ∗∗.
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fig1: Caspase 8 (a) and 9 (b) activities were determined using luminescent kits as described in the method for SK-MEL-28 cell line treated with xanthones for 48 h. The values are shown as the mean ± SEM (n = 3). Treatments significantly different from the untreated control at P < 0.05 are presented as ∗ and at P < 0.01 as ∗∗.

Mentions: A significant increase in caspase 8 after 48 h treatment of SK-MEL-28 cells was observed only with α-mangostin. Treatment with α-mangostin at 5 μg/mL resulted in an approximately 1.6-fold increase (P < 0.05) and at 7.5 μg/mL resulted in an approximately 3-fold increase (P < 0.01) relative to untreated cells (Figure 1(a)).


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

Wang JJ, Zhang W, Sanderson BJ - Biomed Res Int (2013)

Caspase 8 (a) and 9 (b) activities were determined using luminescent kits as described in the method for SK-MEL-28 cell line treated with xanthones for 48 h. The values are shown as the mean ± SEM (n = 3). Treatments significantly different from the untreated control at P < 0.05 are presented as ∗ and at P < 0.01 as ∗∗.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3794626&req=5

fig1: Caspase 8 (a) and 9 (b) activities were determined using luminescent kits as described in the method for SK-MEL-28 cell line treated with xanthones for 48 h. The values are shown as the mean ± SEM (n = 3). Treatments significantly different from the untreated control at P < 0.05 are presented as ∗ and at P < 0.01 as ∗∗.
Mentions: A significant increase in caspase 8 after 48 h treatment of SK-MEL-28 cells was observed only with α-mangostin. Treatment with α-mangostin at 5 μg/mL resulted in an approximately 1.6-fold increase (P < 0.05) and at 7.5 μg/mL resulted in an approximately 3-fold increase (P < 0.01) relative to untreated cells (Figure 1(a)).

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus