Ganoderic Acid Me Inhibits Tumor Invasion Through Down-Regulating Matrix Metalloproteinases 2/9 Gene Expression

Chen, Nianhong; Liu, Jianwen; Zhong, Jian‐Jiang

doi:10.1254/jphs.sc0080019

Cited by 97 publications

(53 citation statements)

References 13 publications

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“…21 Compiled studies have implicated MMPs in cell metastatic potential in physiological and pathological processes through the basis for the mechanism of ECM degradation. Tissue inhibitors of MMPs in general inhibit tumor cell invasion, angiogenesis and metastasis.…”

Section: Muc1 Overexpression Promotes Cell Metastatic Potential Throumentioning

confidence: 99%

MUC1 induces metastasis in esophageal squamous cell carcinoma by upregulating matrix metalloproteinase 13

Zheng

Liao

et al. 2011

Laboratory Investigation

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Esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances because of its high frequency of metastasis. Given the associations of MUC1 with ESCC and tumor metastasis, we explored a potential role of MUC1 in ESCC metastasis. Among 40 ESCC and 20 paired normal tissue specimens examined, we found a significant increase of MUC1 expression in ESCC and more importantly, that expression of MUC1 and MMP13 are strongly correlated in patients who had lymph node metastasis. Studies with cell models indicated that overexpression of MUC1 upregulates the expression of MMP13, leading to increased cell migration. In support of a mode of transcriptional regulation, promoter analysis revealed that MUC1 stimulates MMP13 expression through the Runx-2-binding site. The link of MUC1 to cell motility was further confirmed by the finding that depletion of MUC1 resulted in reduced expression of MMP13 and cell migration, invasion and adhesion. Moreover, the loss of cell metastatic potential was rescued by overexpression of MMP13 completely. Collectively, our findings indicate that MUC1 contributes to ESCC metastasis by stimulating MMP13 expression, suggesting MUC1 as a novel diagnostic biomarker and therapeutic target in ESCC. Esophageal squamous cell carcinoma (ESCC) frequently exhibits extensive local invasion or regional lymph node metastasis at the time of initial diagnosis; therefore, it is one of the most common aggressive diseases with poor outcome. 1 Tumor invasion and metastasis involve degradation of different components of the extracellular matrix and require the actions of proteolytic enzymes, such as matrix metalloproteinases (MMPs), which are produced either by the tumor cells or surrounding stromal cells.2,3 MMP13 is a highly regulated zinc-dependent endopeptidase and has been reported to be associated with vascular invasion and lymph node metastasis in ESCC. 4 Mechanisms involved in regulation of MMP13 in ESCC are likely complex and poorly understood.Mucins are high-molecular-weight glycoproteins that have been identified as markers of adverse prognosis and as attractive therapeutic targets.5 MUC1, one of transmembrane mucins, is normally expressed in esophageal epithelium.Patients with MUC1 high expression often appear with advanced stage or lymph node metastasis suggesting correlation of the MUC1 expression and the invasion or metastasis of ESCC.6 In this study, we investigated the expression of MUC1 and MMP13 in ESCC patients and the potential functional relationship in tumor metastasis and prognosis. MATERIALS AND METHODS Tissue Sample CollectionA total of 40 paraffin-embedded archival specimens of primary ESCC cases were enrolled in this study: 20 with lymph node metastasis and 20 without lymph node metastasis. A total of 20 paired normal esophageal tissue specimens distant from the cancerous lesion in patients without lymph node metastasis were used as control. These patients did not receive any preoperative adjuvant radiation or chemotherapy.

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Section: Muc1 Overexpression Promotes Cell Metastatic Potential Throumentioning

confidence: 99%

MUC1 induces metastasis in esophageal squamous cell carcinoma by upregulating matrix metalloproteinase 13

Zheng

Liao

et al. 2011

Laboratory Investigation

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“…GAMe also effectively inhibited migration of 95-D cells in a dose-and time-dependent manner via induction of actin polymerization. In addition, GA-Me could suppress invasion of 95-D cells by inhibiting MMP2 and MMP9 gene expression [73]. According to the data mentioned above, ganoderic acid was thought to be a potent bioactive compound in G. lucidum.…”

Section: The Triterpenoids Fractionmentioning

confidence: 97%

The in vitro and in vivo experimental evidences disclose the chemopreventive effects of Ganoderma lucidum on cancer invasion and metastasis

Weng

Yen

2010

Clin Exp Metastasis

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The Ganoderma lucidum (Leyss. ex Fr.) Karst, an edible mushroom, has been utilized for centuries in East Asia to prevent or treat various diseases and to reduce the likelihood of cancer invasion and metastasis. The primary bioactive compounds are commonly considered to be polysaccharides and triterpenoids. Evidence that G. lucidum extract and its bioactive compounds may have a potential inhibitory effect on cancer invasion and metastasis is increasingly being reported in the scientific literature. This review assembles and summarizes past publications on the in vitro and in vivo effects of G. lucidum on cancer invasion and metastasis, and concludes that these effects occur through modulation of the phosphorylation of extracellular signal-regulated kinase (ERK1/2), phosphatidylinositol 3-kinase (PI 3-kinase) or Akt kinase (protein kinase B). Activation of these kinases subsequently inhibits the activity or expression of activator protein-1(AP-1) and nuclear factor-kappa B (NF-kappaB), resulting in the down-regulation of urokinase plaminogen activator (uPA), uPA receptor (uPAR), matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta1, interleukin (IL)-8, inducible nitric oxide (NO) and beta1-integrin as shown in various cell lines or animal models. G. lucidum may be an effective nutraceutical used in the prevention of cancer metastasis. To further elucidate the bioactive components present in G. lucidum and the anti-metastatic mechanisms underlying these compounds, more in vitro and in vivo tests as well as clinical trials are necessary.

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“…Studies showed that Ganoderic acid extracted from G. lucidum suppressed invasion of 95-D, LLC, and HCT-116 metastatic cancer cells via inhibition of MMP-9 expression [48,49].…”

Section: Reduced Metastatic Potentialmentioning

confidence: 99%

Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways

Jesuthasan

Bishop

Glucina³

et al. 2013

FFHD

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Ganoderma lucidum, commonly referred to as Lingzhi, has been used in Asia for health promotion for centuries. The anti-cancer effects of G. lucidum have been demonstrated in both in vitro and in vivo studies. In addition, the observed anti-cancer activities of Ganoderma have prompted its usage by cancer patients alongside chemotherapy.The main two bioactive components of G. lucidum can be broadly grouped into triterpenes and polysaccharides. Despite triterpenes and polysaccharides being widely known as the major active ingredients, the different biological pathways by which they exert their anti-cancer effect remain poorly defined. Therefore, understanding the mechanisms of action may lead to more widespread use of Ganoderma as an anti-cancer agent.The aim of this paper is to summarise the various bioactive mechanisms that have been proposed for the anti-cancer properties of triterpenes and polysaccharides extracted from G. lucidum. A literature search of published papers on NCBI with keywords "Ganoderma" and "cancer" was performed. Among those, studies which specifically examined the anti-cancer activities of Ganoderma triterpenes and polysaccharides were selected to be included in this paper.We have found five potential mechanisms which are associated with the anti-cancer activities of Ganoderma triterpenes and three potential mechanisms for Ganoderma polysaccharides. In addition, G. lucidum has been used in combination with known anti-cancer agents to improve the anti-cancer efficacies. This suggests Ganoderma's bioactive pathways may compliment that of anti-cancer agents. In this paper we present several potential anti-cancer mechanisms of Ganoderma triterpenes and polysaccharides which can be used for the development of Ganoderma as an anti-cancer agent.

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Ganoderic Acid Me Inhibits Tumor Invasion Through Down-Regulating Matrix Metalloproteinases 2/9 Gene Expression

Cited by 97 publications

References 13 publications

MUC1 induces metastasis in esophageal squamous cell carcinoma by upregulating matrix metalloproteinase 13

MUC1 induces metastasis in esophageal squamous cell carcinoma by upregulating matrix metalloproteinase 13

The in vitro and in vivo experimental evidences disclose the chemopreventive effects of Ganoderma lucidum on cancer invasion and metastasis

Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways

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