α-Mangostin Induces Apoptosis in Human Chondrosarcoma Cells through Down-regulation of ERK/JNK and Akt Signaling Pathway

Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand.
Journal of Agricultural and Food Chemistry (Impact Factor: 2.91). 03/2011; 59(10):5746-54. DOI: 10.1021/jf200620n
Source: PubMed


Chondrosarcoma is a malignant primary bone tumor that is resistant to chemotherapy and radiation therapy. α-Mangostin, a component of Garcinia mangostana Linn, is a xanthone derivative shown to have antioxidant and antitumor properties. This study is the first to investigate anticancer effects of α-mangostin in the human chondrosarcoma cell line SW1353. We showed that α-mangostin inhibited cell proliferation of SW1353 cells in a time- and dose-dependent manner by using the trypan blue exclusion method. Hoechst 33342 nuclear staining and nucleosomal DNA-gel electrophoresis revealed that α-mangostin could induce nuclear condensation and fragmentation, typically seen in apoptosis. Flow cytometry using Annexin V/PI double staining assessed apoptosis, necrosis and viability. α-Mangostin activated caspase-3, -8, -9 expression, decreased Bcl-2 and increased Bax. This promotes mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytoplasm. In addition, total and phosphorylated ERK and JNK were downregulated in α-mangostin-treated SW1353 cells but no changes in p38. α-Mangostin also decreased phosphorylated Akt without altering total Akt. These results suggest that α-mangostin inhinbited cell proliferation and induced apoptosis through downregulation of ERK, JNK and Akt signaling pathway in human chondrosarcoma SW1353 cells.

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    • "The ERKs pathway is upregulated in human tumors and, as such, represents an attractive target for anticancer therapy [39, 40]. The phosphorylation of ERKs results in their nuclear translocation and activation of numerous substrates, promoting proliferation and inhibiting proapoptotic signals [41]. "
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    ABSTRACT: Liquiritigenin (LQ), separated from Glycyrrhiza radix, possesses anti-inflammatory, antihyperlipidemic, and antiallergic effects. Our present study aims to investigate the antihepatocellular carcinoma effects of LQ both in cell and animal models. LQ strikingly reduced cell viability, enhanced apoptotic rate, induced lactate dehydrogenase over-release, and increased intracellular reactive oxygen species (ROS) level and caspase 3 activity in both PLC/PRL/5 and HepG2 cells. The expression of cleaved PARP, the hall-marker of apoptosis, was enhanced by LQ. LQ treatment resulted in a reduction of the expressions of B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xL), and an increase of the phosphorylation of c-Jun N-terminal kinases (JNK) and P38. LQ-mediated cell viability reduction, mitochondrial dysfunction, apoptosis related protein abnormal expressions, and JNK and P38 activation were partially abolished by N-Acetyl-L-cysteine (a ROS inhibitor) pretreatment. Moreover, LQ suppressed the activation of extracellular signaling-regulated kinase (ERKs) and reduced the translocation of phosphor-ERKs from cytoplasm to nucleus. This antitumor activity was further confirmed in PLC/PRL/5-xenografted mice model. All these data indicate that the antihepatocellular carcinoma effects of LQ are related to its modulation of the activations of mitogen-activated protein kinase (MAPKs). The study provides experimental evidence supporting LQ as a potential therapeutic agent for hepatocellular carcinoma treatment.
    03/2014; 2014(6):965316. DOI:10.1155/2014/965316
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    • "This is consistent with the studies of Matsumoto et al. [36] and Wang et al. [8]. In contrast, Krajarng et al. [35] found that α-mangostin increased Bax protein expression and decreased Bcl-2 in human chondrosarcoma SW1353 cell line. Thus, the effect of α-mangostin appears to be cancer type dependent. "
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    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 μ g/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, NF κ B, and I κ B α ). α -Mangostin significantly upregulated mRNA expression of cytochrome C and p21(WAF1) and downregulated that of cyclin D1, Akt1, and NF κ B. γ -Mangostin significantly downregulated mRNA expression of Akt1 and NF κ B and upregulated p21(WAF1) and I κ B α . 8-Deoxygartanin significantly upregulated the mRNA expression of p21(WAF1) and downregulated that of cyclin D1 and NF κ B. 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.
    09/2013; 2013(5392):715603. DOI:10.1155/2013/715603
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    • "These include optimization of pressure, temperature , and solvent to material ratio in supercritical carbon extraction (Zarena et al., 2010). Despite various trials, the maceration solvent extraction is still the most commonly used method for phenolic compounds extraction from mangosteen hull in pharmaceutical studies (Balunas et al., 2008; Kaomongkolgit et al., 2011; Krajarng et al., 2011; Watanapokasin et al., 2010). The maceration solvent extraction of phenolic compounds from plant material is influenced by factors such as extraction time, solid to solvent ratio, solvent concentration, etc. which can be optimized. "
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    ABSTRACT: The optimum conditions of extraction time, solid to solvent ratio, and methanol concentration for extracting total phenolic content (TPC) from mangosteen (Garcinia mangostana L.) hull powder have been investigated using response surface methodology. The experimental data obtained was adequately fitted into second-order polynomial models with coefficient of determination (R2) of 0.897. Response surface analysis showed that the optimal extraction parameters which gave a maximum TPC yield of 140.66 mg gallic acid equivalent (GAE)/g powder were from a 2 h extraction with 0.05 solid to solvent ratio and at 69.77% methanol concentration. Analysis using artificial neural network (ANN) predicted data which showed a higher R2 value of 0.945 and average absolute deviation (ADD) values of 4.01% versus 5.37% for the RSM. This suggests that ANN is a better modelling technique for nonlinear data for predicting TPC extracted from mangosteen hull powder compared to the response surface methodology (RSM).
    Industrial Crops and Products 11/2012; 40(1):247–253. DOI:10.1016/j.indcrop.2012.03.019 · 2.84 Impact Factor
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