Ginsenoside Rg3 inhibits CXCR4 expression and related migrations in a breast cancer cell line

Chen, Xiaoping; Qian, Linlin; Jiang, Hong; Chen, Jianghua

doi:10.1007/s10147-011-0222-6

Cited by 46 publications

(27 citation statements)

References 38 publications

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“…The high level of CXCR4 mRNA in tumor cells is believed to be involved in their survival under hypoxia [28]. Further, overexpression of CXCR4 has been associated with metastases formation and poor prognosis of patients with breast and other types of cancer [29][30][31], which explains the significant interest towards CXCR4 inhibitors [32,33].…”

Section: Discussionmentioning

confidence: 99%

“…The equal levels of CXCR4 in treated and control MCF10A cells at 7h implied that the reduction in expression of CXCR4 in these cells required more time. Even though there are no data about saponins from TT, CXCR4 downregulation at protein level has been detected after treatment of cells with saponins extracted from various other plants like ginseng [32].…”

Section: Discussionmentioning

confidence: 99%

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Changes in gene expression of CXCR4, CCR7 and BCL2 after treatment of breast cancer cells with saponin extract from Tribulus terrestris

Goranova¹,

Ss²,

Vs³

et al. 2015

neo

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Saponins are natural substances produced by a large number of plants, one of which is Tribulus terrestris L. (TT). They have been reported to possess an antitumor activity exerted by regulating various signaling pathways in the cell. Although the mechanisms of action of saponin extracts from various plants have been widely studied, limited data are available about TT. The present study aimed to analyze the impact of saponin extract from TT on cell processes in breast carcinoma cell lines. The variations in expression of a group of 32 selected genes were examined by real-time PCR after saponin treatment of MCF7 and MCF10A cell lines. Only three genes -CXCR4, CCR7 and BCL2, showed changes in their mRNA levels after the application of the herb extract. While CXCR4 expression was reduced in both cell lines, CCR7 and BCL2 levels decreased only in tumorigenic MCF7 cells, implying cell-specificity of the saponin action. Our results suggested that TT extract containing saponins was likely to affect the processes of apoptosis and metastasizing of cancer cells. Further in vivo studies will show its applicability as an anticancer therapeutic agent.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Changes in gene expression of CXCR4, CCR7 and BCL2 after treatment of breast cancer cells with saponin extract from Tribulus terrestris

Goranova¹,

Ss²,

Vs³

et al. 2015

neo

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“…Ginsenoside Rg3 combined with capecitabine enhanced antiangiogenic efficacy in breast cancer in mice and exhibited improved antitumor effects and reduced toxicity (15). In addition, ginsenoside Rg3 was shown to inhibit CXCR4 expression and related migrations in the MDA-MB-231 breast cancer cell line (16). Rg3 promoted the efficacy of cisplatin by inhibiting heme oxygenase 1 and NAD(P)H dehydrogenase (quinone 1) expression in CT-26 colon cancer cells and protected the kidney and liver against tissue damage by preventing cisplatin-induced intracellular reactive oxygen species generation (17).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg3 enhances the inhibitory effects of chemotherapy on esophageal squamous cell carcinoma in mice

Chang

Huo

et al. 2014

Molecular and Clinical Oncology

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Abstract. The present study was conducted in order to investigate the inhibitory effects of ginsenoside Rg3 combined with chemotherapy on Eca-109 esophageal squamous cell carcinoma (ESCC) in mice. Tumor xenograft models were established in the right forelimb of 20 BALB/c nude mice by subcutaneous injection. The tumor-bearing mice were randomly assigned to 4 treatment groups (n=5 per group) as follows: the control group (saline), the ginsenoside Rg3 alone group (6 mg/kg/day, once a day for 3 weeks), the chemotherapy alone group (paclitaxel 10 mg/kg/day + cisplatin 5 mg/kg/day on days 1, 7, 14 and 21) and the chemotherapy + Rg3 group (combined treatment). The length and width of the tumor were directly measured with calipers at different time points and the tumor volume (cm 3 ) was calculated using the formula 0.52 x length x width 2 every other day. The mice were sacrificed by cervical dislocation following completion of therapy, the tumors were removed and weighed and the expression levels of Ki-67 were determined by immunohistochemistry. The results indicated that the coadministration of ginsenoside Rg3 significantly enhanced the inhibitory effects of chemotherapy on tumor growth. In addition, the expression levels of Ki-67 in the chemotherapy + Rg3 group were significantly lower compared to those in the other 3 groups. The chemotherapy + Rg3 group also exhibited the lowest microvascular density among all four groups. These findings suggested that ginsenoside Rg3 may improve the antitumor efficacy of chemotherapy in Eca-109 ESCC in mice.

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“…Using indirect investigational techniques, the influence of Rg3 on CXCR4 expression has been reported in cultured MDA-MB-231 breast cancer cell line (Chen et al 2011). Based on Immunohistochemistry, chemotaxis, and wound healing mobility assays, it has been shown that Rg3 treatment at nontoxic dose range elicits a weak CXCR4 staining indicative of downregulation of the receptor, concomitant with diminutions in the number of migrated cells in CXCL12-elicited chemotaxis, and reduction in the width of the scar in wound healing assay attesting Rg3 efficacy with CXCR4 inhibition (Chen et al 2011). …”

Section: Chemokine Receptors and Microenvironmentmentioning

confidence: 99%

Pivotal Role of Chemokine Receptor Signaling Axis and Natural Bioactive Chemopreventive Agents in Metastasis of Breast Cancer

Banerjee

Paruthy

Rajamani

et al. 2016

Critical Dietary Factors in Cancer Chemoprevention

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Breast cancer ranks as one of the most frequently diagnosed malignant neoplasm in women embracing multiple genomic alterations that influence tumor growth, progression, and metastasis. Despite significant advancements in systemic adjuvant chemotherapy for breast cancer, manifestations of distant metastasis raise significant clinical problems with worst prognosis. Therefore, defining molecular events underlying metastasis alongside well defined strategic abrogation of these molecular events is crucial for improving patient survival and better clinical management. The classic "seed and soil" hypothesis of tumor metastasis has been redefined in light of emerging evidence revealing chemokine [CXCL12 (SDF-1α)] and its cognate receptor (CXCR4) orchestrating signaling events that guide chemotaxis of tumor cells to site of metastasis. CXCR4 is a transmembrane G proteincoupled receptor reportedly overexpressed in primary and metastatic breast tumors compared to normal breast tissue, and its chemokine ligand (SDF-1α) presents peak expression in common metastatic sites. CXCR4-SDF-1α signaling has earned considerable attention underscoring its role in cancer metastasis including activation of focal clusters of integrin and adhesion kinase (Rho/ROCK) and multiple signaling entities (Cdc42, PI3K-Akt, p38 MAPK) that allow tumor cells to attain a migratory phenotype. Hypoxia, vascular endothelial growth factor (VEGF), transcription factor NF-κB, and estrogen receptor status upregulates CXCR4 expression in tumor microenvironment. A growing body of evidence suggests that natural chemo-dietary agents hold prospect targeting CXCR4-SDF-1α axis to prevent metastasis of breast cancer. This chapter presents a succinct overview about CXCR4 receptor signaling in breast cancer and related mechano-transductive pathways, microenvironmental cues, and current status and knowledge regarding efficacy of bioactive natural products on metastasis and homing of malignant tumor cells.

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Ginsenoside Rg3 inhibits CXCR4 expression and related migrations in a breast cancer cell line

Abstract: This work suggests that Rg3 is a new CXCR4 inhibitor from a natural product.

Cited by 46 publications

References 38 publications

Changes in gene expression of CXCR4, CCR7 and BCL2 after treatment of breast cancer cells with saponin extract from Tribulus terrestris

Changes in gene expression of CXCR4, CCR7 and BCL2 after treatment of breast cancer cells with saponin extract from Tribulus terrestris

Ginsenoside Rg3 enhances the inhibitory effects of chemotherapy on esophageal squamous cell carcinoma in mice

Pivotal Role of Chemokine Receptor Signaling Axis and Natural Bioactive Chemopreventive Agents in Metastasis of Breast Cancer

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