A Novel Carbohydrate-Based Therapeutic GCS-100 Overcomes Bortezomib Resistance and Enhances Dexamethasone-Induced Apoptosis in Multiple Myeloma Cells

Chauhan, Dharminder; Li, Guilan; Podar, Klaus; Hideshima, Teru; Neri, Paola; He, Deli; Mitsiades, Nicholas; Richardson, Paul G.; Chang, Yan; Schindler, Joanne; Carver, Bradley; Anderson, Kenneth C.

doi:10.1158/0008-5472.can-05-0163

Cited by 142 publications

(103 citation statements)

References 45 publications

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“…Furthermore, increased plasma galectin-3 levels have been reported in (metastasized) cancer [4,5,13,14,[28][29][30]], Behçet's disease [7] and obesity [8], and galectin-3 levels may even guide therapy [14]. We hypothesize that deleterious signals that precede overt disease initiate subclinical tissue changes associated with galectin-3 activation and secretion.…”

Section: Discussionmentioning

confidence: 96%

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The fibrosis marker galectin‐3 and outcome in the general population

Boer¹,

Veldhuisen²,

Gansevoort³

et al. 2011

Journal of Internal Medicine

324

290

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Abstract. de Boer RA, van Veldhuisen DJ, Gansevoort RT, Muller Kobold AC, van Gilst WH, Hillege HL, Bakker SJL, van der Harst P (University of Groningen). The fibrosis marker galectin-3 and outcome in the general population. J Intern Med 2012; 272: 55-64.Objective. Galectin-3 is involved in fibrosis and inflammation and plays a role in heart failure, renal disease, obesity and cancer. We aimed to establish the relationship between galectin-3 and cardiovascular (CV) risk factors and mortality in the general population.Design and subjects. This study included 7968 subjects from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort, with a median follow-up of approximately 10 years. Plasma galectin-3 was measured in baseline samples.Main outcome measures. We investigated the relationships between galectin-3 levels, demographic characteristics and risk factors of CV disease. We determined the prognostic value for all-cause, CV and cancer mortality.Results. The mean age of the population was 50 ± 13 years. Mean blood pressure was 129 ⁄ 74 mmHg, mean cholesterol was 5.7 ± 1.1 mmol L )1 and median galectin-3 was 10.9 ng mL )1 [interquartile range (IQR) 9.0-13.1]. Galectin-3 levels correlated with a wide range of risk factors of CV disease, including blood pressure, serum lipids, body mass index, renal function and N-terminal pro-B-type natriuretic peptide (P < 0.0001). We observed a strong association between galectin-3 and age. Furthermore, we found a gender interaction, with female subjects (n = 4001) having higher median galectin-3 levels (11.0 ng mL )1 , IQR 9.1-13.4 vs. men (n = 3967) 10.7 ng mL )1 , IQR 8.9-12.8; P < 0.0001), and galectin-3 levels in women more strongly correlated with risk factors of CV disease. After correction for the classical CV risk factors (smoking, blood pressure, cholesterol and diabetes), galectin-3 levels independently predicted all-cause mortality (hazard ratio per SD galectin-3 1.09, 95% CI 1.01-1.19; P = 0.036), but not CV and cancer mortality separately.Conclusions. Galectin-3 is associated with age and risk factors of CV disease, with a strong gender interaction for these correlations. Galectin-3 predicts all-cause mortality in the general population.

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Section: Discussionmentioning

confidence: 96%

“…Further mechanistic studies should be conducted to unravel how galectin-3 is activated and secreted. This may have clinical importance, as galectin-3-targeted therapy has been proposed as a therapeutic option in diseases associated with increased galectin-3 levels [30].…”

Section: Discussionmentioning

confidence: 99%

The fibrosis marker galectin‐3 and outcome in the general population

Boer¹,

Veldhuisen²,

Gansevoort³

et al. 2011

Journal of Internal Medicine

324

290

View full text Add to dashboard Cite

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“…From these studies it is clear that pectin, CP and MCP, as a galectin-3 inhibitor, may hold a significant role in cancer chemotherapy. Interestingly, it has been demonstrated that inhibition of galectin-3 by MCP reverses multiple myeloma cell resistance to bortezomib and enhances apoptosis induced by dexamethasone (Chauhan et al, 2005). Similarly, dose dependent exposure of hemangiosarcoma cells to MCP increases their sensitivity towards doxorubicin and induces apoptosis (Johnson et al, 2007) suggesting that inactivation of galectin-3 by MCP increases sensitivity of cancer cells towards chemotherapeutic agents.…”

Section: Mcp and Chemotherapymentioning

confidence: 99%

Plant Pectin: A Potential Source for Cancer Suppression

Niture¹

2013

American Journal of Pharmacology and Toxicology

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Pectin is a branched polysaccharide present widely in a variety of fruits. It has been of high interest to cancer biologists due to its involvement in metal/carcinogen detoxification and its anti-carcinogenic properties. In particular, Citrus Pectin (CP) and Modified Citrus Pectin (MCP) have been shown to have a significant inhibitory role in cancer cell metastasis, invasion, angiogenesis and survival. The interactions and inactivation of oncogenes by CP and MCP in prostate, breast, liver, lung, melanoma and multiple myeloma cancers suggest that CP and MCP could play an important role in cancer chemotherapy and chemoprevention. In this review, we focus on the biological function of pectin with respect to its properties, sources, structure and its potential role in carcinogen detoxification and cancer suppression.

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“…Among these pectin-based inhibitors, MCP has attracted special attention. Studies from several groups have shown that MCP inhibits multiple steps of tumor metastasis via inhibition of galectin-3 including inhibition of cancer cell adhesion, homotypic aggregation, invasion, clonogenic survival, angiogenesis, sensitization of neoplastic cells to apoptosis induced by chemotherapeutic agents, and correction of the impaired function of tumor-infiltrating lymphocytes (20,(23)(24)(25)(26)(27)(28).…”

mentioning

confidence: 99%

The Inhibitory Effects of a Rhamnogalacturonan Ι (RG-I) Domain from Ginseng Pectin on Galectin-3 and Its Structure-Activity Relationship

Gao

Yang

Sun

et al. 2013

Journal of Biological Chemistry

116

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Background: Structural elements in pectin that inhibit galectin-3, a ␤-galactoside-binding protein associated with cancer progression, are poorly defined. Results: Both backbone and side chains of pectin RG-I-4 were important for its anti-galectin-3 activity. Conclusion: High activity of RG-I-4 was due to cooperation between short ␤1,4-galactan side chains. Significance: The results are valuable for producing highly active pectin-based galectin-3 inhibitors.

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A Novel Carbohydrate-Based Therapeutic GCS-100 Overcomes Bortezomib Resistance and Enhances Dexamethasone-Induced Apoptosis in Multiple Myeloma Cells

Abstract: Human multiple myeloma is a presently incurable hematologic malignancy, and novel biologically based therapies are urgently needed.

Cited by 142 publications

References 45 publications

The fibrosis marker galectin‐3 and outcome in the general population

The fibrosis marker galectin‐3 and outcome in the general population

Plant Pectin: A Potential Source for Cancer Suppression

The Inhibitory Effects of a Rhamnogalacturonan Ι (RG-I) Domain from Ginseng Pectin on Galectin-3 and Its Structure-Activity Relationship

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