Involvement of matrix metalloproteinase 2 and 9 in gambogic acid induced suppression of MDA-MB-435 human breast carcinoma cell lung metastasis

Qi, Qi; Gu, Hong-Yan; Yang, Yong; Lu, Na; Zhao, Jie; Liu, Wei; Liu, Hua; Qin, You; Wang, Xiaotang; Guo, Qinglong

doi:10.1007/s00109-008-0398-z

Cited by 55 publications

(35 citation statements)

References 47 publications

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“…24) Briefly, 200 µL of cell suspension (1.9×10 4 cells/well) were seeded into 96-well plates (Costar, Cambridge, MA, U.S.A.) and incubated at 37°C. After 24 h incubation, cells were treated with 0-8 µM of isomorellin in triplicate for 0, 24, 48 or 72 h. Since gambogic acid coexists with isomorellin in the same plant and is a well-known caged xanthone having potent anticancer effects, [16][17][18][19][20][21][22] 0-8 µM of gambogic acid was used as a reference compound for treating cells. Doxorubicin and 0.1% DMSO were used as the positive and negative controls, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…anti-angiogenesis 19) and an anti-invasive effect 20) by gambogic acid have been reported. In addition, gambogic acid has been shown to induce cell cycle arrest at the G2/M phase in human gastric carcinoma BGC-823 cells.…”

Section: )mentioning

confidence: 99%

“…21) Owing to these significant anti-tumor activities, the Chinese Food and Drug Administration recently approved a phase II clinical trial of gambogic acid injection as an antitumor treatment. 20) It is therefore possible that other caged xanthones inhibit cancer cell growth and/or induce apoptosis through modulation of NF-κB expression and induction of cell cycle arrest.…”

Section: )mentioning

confidence: 99%

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Involvement of p53 and Nuclear Factor-kappaB Signaling Pathway for the Induction of G1-Phase Cell Cycle Arrest of Cholangiocarcinoma Cell Lines by Isomorellin

Hahnvajanawong

Ketnimit

Pattanapanyasat

et al. 2012

Biological & Pharmaceutical Bulletin

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Cell cycle arrest is closely linked to apoptosis. Isomorellin-a caged xanthone isolated from Garcinia hanburyi-induced apoptosis in cholangiocarcinoma (CCA) cell lines. To elucidate potential anticancer mechanisms, we investigated the effects of isomorellin on the growth, cell cycle progression, cell cycle regulated protein expression and nuclear factor-kappa B (NF-κB) activation of KKU-100 and KKU-M156 CCA cell lines; using sulforhodamine B assay, flow cytometry and Western blot analysis. The growth of both CCA cell lines was significantly inhibited by isomorellin treatment in a time-and dose-dependent manner. The respective IC 50 value of isomorellin for KKU-100 cells was 6.2 0.13, 5.1 0.11 and 3.5 0.25 µM at 24, 48 and 72 h. By comparison, the respective IC 50 value for KKU-M156 cells was 1.9 0.22, 1.7 0.14 and 1.5 0.14 µM at 24, 48 and 72 h. The growth inhibition of CCA cells by isomorellin was through the G0/G1 phase arrest mediated by inhibition of NF-κB activation, up-regulation of p53, p21 and p27 and down-regulation of cyclin D1, cyclin E, Cdk4 and Cdk2 protein levels. Our research suggests that isomorellin induces cell cycle arrest and apoptosis in CCA cell lines through p53 and the NF-κB-signaling pathway. The growth inhibitory potential of isomorellin was comparable to that of gambogic acid. Isomorellin shows potential as a therapeutic agent against human cholangiocarcinoma.

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Section: Methodsmentioning

confidence: 99%

Section: )mentioning

confidence: 99%

Section: )mentioning

confidence: 99%

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Involvement of p53 and Nuclear Factor-kappaB Signaling Pathway for the Induction of G1-Phase Cell Cycle Arrest of Cholangiocarcinoma Cell Lines by Isomorellin

Hahnvajanawong

Ketnimit

Pattanapanyasat

et al. 2012

Biological & Pharmaceutical Bulletin

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“…12, 14 Wang et al 15 describe the potential role of GA to reverse docetaxel resistance though downregulation of survivin in gastric cancer cells. Survivin might play a key role in MDR in the presence of P-gp, and this might represent a novel strategy for modulating MDR in cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Poloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer

Saxena¹,

Hussain²

2012

IJN

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Background: Delivery of a high concentration of anticancer drugs specifically to cancer cells remains the biggest challenge for the treatment of multidrug-resistant cancer. Poloxamers and D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) are known inhibitors of P-glycoprotein (P-gp). Mixed micelles prepared from Poloxamer 407 and TPGS may increase the therapeutic efficacy of the drug by delivering high concentrations inside the cells and inhibiting P-gp. Gambogic acid (GA) is a naturally derived novel anticancer agent, but poor solubility and toxic side effects limit its use. In this study, we have developed Poloxamer 407 and TPGS mixed micelle-encapsulating GA for the treatment of breast and multidrug-resistant cancer. Methods: GA-loaded Poloxamer 407/TPGS mixed micelles were prepared using a thin film hydration method, and their physicochemical properties were characterized. Cellular accumulation and cytotoxicity of the GA-loaded Poloxamer 407/TPGS mixed micelles were studied in breast cancer cells, MCF-7 cells, and multidrug-resistant NCI/ADR-RES cells. Results:The diameter of GA-loaded Poloxamer 407/TPGS mixed micelles was about 17.4 ± 0.5 nm and the zeta potential -13.57 mV. The entrapment efficiency of GA was 93.1% ± 0.5% and drug loading was about 9.38% ± 0.29%. Differential scanning calorimetry and X-ray powder diffraction studies confirmed that GA is encapsulated by the polymers. The in vitro release studies showed that mixed micelles sustained the release of GA for more than 4 days. Results from cellular uptake studies indicated that GA-loaded Poloxamer 407/TPGS mixed micelles had increased cellular uptake of GA in NCI/ADR-RES cells. Cytotoxicity of GA-loaded Poloxamer 407/TPGS mixed micelles was found to be 2.9 times higher in multidrug-resistant NCI/ADR-RES cells, and 1.6 times higher in MCF-7 cells, as compared with unencapsulated GA. Conclusion: This study suggests that Poloxamer 407/TPGS mixed micelles can be used as a delivery system for GA to treat breast and multidrug-resistant cancer.

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“…Gambogic acid is the most intensively studied caged xanthone, and exhibits potent antitumor activity in vitro and in vivo (11)(12)(13) through several mechanisms, including inhibition of topoisomerase II alpha activity (14), downregulation of telomerase (15), induction of cell cycle arrest (16) and induction of apoptosis (17). Due to its low toxicity against normal tissues (18,19), gambogic acid is now approved for a phase II clinical trial in China (20).…”

Section: Introductionmentioning

confidence: 99%

Antitumor effect of forbesione isolated from Garcinia hanburyi on cholangiocarcinoma in vitro and in vivo

et al. 2016

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Abstract. Cholangiocarcinoma (CCA) is a malignancy with no effective therapy and poor prognosis. Forbesione, a caged xanthone isolated from Garcinia hanburyi, has been reported to inhibit proliferation and to induce apoptosis in human CCA cell lines. The present study aimed to further explore the potential anticancer properties of forbesione by testing its effects against the hamster CCA cell line Ham-1 in vitro and in vivo. It was observed that forbesione inhibited the growth of Ham-1 cells in vitro and suppressed Ham-1 growth as allograft in hamsters by inducing cell cycle arrest at the S phase. This was mediated by decreasing the protein expression of cyclin E, cyclin A and cyclin-dependent kinase 2. In addition, increased expression of p21 and p27 was detected, which could possibly explain the reduced expression of proliferating cell nuclear antigen and of the bile duct cell marker cytokeratin 19 observed in forbesione-treated Ham-1 cells in vitro and in tumor tissues of forbesione-treated hamsters. Furthermore, forbesione induced apoptosis through multiple pathways. The death receptor pathway was activated by increased expression of Fas, Fas-associated death domain and activated caspase-3, along with decreased expression of procaspase-8 and procaspase-3. The mitochondrial pathway was driven by increased expression of B-cell lymphoma (Bcl)-2-like protein 4, activated caspase-9 and inhibitor of κB-α, along with decreased expression of Bcl-2, survivin, procaspase-9 and nuclear factor-κB/p65. The endoplasmic reticulum pathway was stimulated by increased expression of activated caspase-12 and decreased expression of procaspase-12. No side effects or toxicity were observed in forbesione-treated hamsters. Thus, forbesione is a potential drug candidate for cancer therapy that deserves further investigation. IntroductionCholangiocarcinoma (CCA), the malignant tumor of biliary epithelial cells, is the cancer of highest incidence in northeastern Thailand (1), and has increasing incidence and mortality worldwide (2,3). More than 70% of CCA patients have an advanced stage of the disease at the time of diagnosis, which makes curative surgical resection unfeasible (4). In these advanced CCA patients, chemotherapy is the usual treatment option (5). The systemic chemotherapy choices currently offered are 5-fluorouracil (5-FU), carboplatin plus 5-FU, gemcitabine and paclitaxel, which have failed to improve survival, and response rates are only ~20% (4). New therapeutic agents for CCA are urgently required.In the past few decades, natural bioactive substances derived from plants have been considered as important antitumor drug sources (6). Forbesione is a caged xanthone isolated from the resin and fruits of Garcinia hanburyi Hook. f. (family Guttiferae), which have been used in Thai traditional medicine (6,7). Gambogic acid, forbesione, isomorellin and isomorellinol, the caged xanthones isolated from G. hanburyi, are reported to exhibit antitumor activities (8) and cytotoxic effects in several cancer cell lines (8-10). Gambog...

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Involvement of matrix metalloproteinase 2 and 9 in gambogic acid induced suppression of MDA-MB-435 human breast carcinoma cell lung metastasis

Cited by 55 publications

References 47 publications

Involvement of p53 and Nuclear Factor-kappaB Signaling Pathway for the Induction of G1-Phase Cell Cycle Arrest of Cholangiocarcinoma Cell Lines by Isomorellin

Involvement of p53 and Nuclear Factor-kappaB Signaling Pathway for the Induction of G1-Phase Cell Cycle Arrest of Cholangiocarcinoma Cell Lines by Isomorellin

Poloxamer 407/TPGS mixed micelles for delivery of gambogic acid to breast and multidrug-resistant cancer

Antitumor effect of forbesione isolated from Garcinia hanburyi on cholangiocarcinoma in vitro and in vivo

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