Expression of γ-glutamyltransferase in cancer cells and its significance in drug resistance

Pompella, Alfonso; Tata, Vincenzo De; Paolicchi, Aldo; Zunino, Franco

doi:10.1016/j.bcp.2005.10.005

Cited by 257 publications

(201 citation statements)

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“…Experimental evidence has elucidated the ability of cellular GGT to modulate crucial redox-sensitive functions, such as antioxidant/antitoxic defences and cellular proliferative/apoptotic balance, and its role in tumor progression, invasion and drug resistance has repeatedly been suggested. [20][21][22][23] GGT is constitutively expressed in several organs and is often significantly increased in malignant or premalignant lesions, where it is considered a factor conferring growth and survival advantages for the rapidly dividing neoplastic cells. 40,41 The ability of cellular GGT to affect the catabolism of extracellular GSH potentially reflects on several aspects of cell metabolism, especially through the modulation of redox status at cell surfaces and H 2 O 2 production.…”

Section: Discussionmentioning

confidence: 99%

“…Several experimental models have elucidated the ability of cellular GGT to modulate crucial redoxsensitive functions, such as antioxidant/antitoxic defences and cellular proliferative/apoptotic balance, and its role in tumor progression, invasion and drug resistance has been proposed. [20][21][22][23] In addition, a potentially interesting interpretation subsumes GGT as a biomarker of exposure to certain cancer-causing xenobiotics, including persistent organic pollutants (POPs). Based on NHANES data, Lee and colleagues 24,25 recently showed that some environmental pollutants such as lead, cadmium, dioxins or organochlorine pesticides are positively and monotonically related to serum GGT levels in the general US population.…”

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confidence: 99%

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Prospective study of the association of gamma‐glutamyltransferase with cancer incidence in women

Strasak

Pfeiffer

Klenk

et al. 2008

Intl Journal of Cancer

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Although several epidemiologic studies have shown that gammaglutamyltransferase (GGT) is associated with cardiovascular disease and all-cause mortality, its relationship with cancer incidence remains widely unexplored. In experimental models the ability of cellular GGT to modulate crucial redox-sensitive functions has been established, and it may thus play a role in tumor progression. In the present study, we investigated the association of GGT with overall and site-specific cancer incidence in a population-based cohort of 92,843 Austrian women with 349,674 serial GGT measurements, prospectively followed-up for a median of 13.5 years. The relationship between GGT and cancer incidence was analyzed using adjusted Cox regression models with age as underlying time metric with age as underlying time metric including GGT concentrations at baseline and incorporating repeated GGT measurements as a time-dependent variable. During follow-up, 4,884 incidence cancers were observed. Compared to normal low GGT (<17.99 U/L), cancer risk was elevated for all other GGT categories (p for trend < 0.0001), with adjusted hazard ratios (95% confidence intervals) of 1.06 (0.99-1.13) for GGT levels between 18.00 and 35.99 U/L (normal high), 1.12 (1.02-1.22) for GGT levels between 36.00 and 71.99 U/L (elevated) and 1.43 (1.28-1.61) for highly elevated GGT (>72.00 U/L). Very similar results were seen when GGT was analyzed as a time-dependent variable. In cancer-site specific models, elevated GGT statistically significantly increased the risk for malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, breast and female genital organs and lymphoid and haematopoietic cancers (all, p < 0.006). Our study is the first to demonstrate in a large population-based cohort that high GGT levels significantly increased cancer risk in women.Published 2008 Wiley-Liss, Inc. This article is a US Government work, and, as such, is in the public domain in the United States of America.Key words: gamma-glutamyltransferase; cancer incidence; risk factor; epidemiology; women Gamma-glutamyltransferase (GGT), present on the external surface of most cells and in serum, is the enzyme responsible for the extracellular catabolism of glutathione (GSH), the main thiol antioxidant in mammalian cells. 1,2 In clinical practice, GGT is commonly used as a diagnostic test to assess liver dysfunction, and as a biological marker of excessive alcohol intake. 1,3,4 However, several recent epidemiologic studies have shown elevated GGT to independently influence morbidity and mortality from causes other than liver disease. Particularly, GGT was independently related to cardiovascular disease, 5-12 it correlated with most cardiovascular risk factors [13][14][15][16] and, more recently, an association with chronic kidney disease was found. 17 In addition, several large-scale studies indicate an independent role of GGT for premature death from all causes. 9,18,19 The association of GGT with cancer incidence, however, remains largely unexplored. Several ex...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Prospective study of the association of gamma‐glutamyltransferase with cancer incidence in women

Strasak

Pfeiffer

Klenk

et al. 2008

Intl Journal of Cancer

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“…The membrane bound enzyme GGT is expressed highly in embryo livers and decreases rapidly to lowest levels after birth. GGT is highly re-expressed during the development of (HCC) Hepatocellular carcinoma (Pompella et al, 2006;Lei et al, 2012). Treatment with A.nilotica significantly lowered the enhanced level of γ-GT in tumor bearing animals when compare to tumor control.…”

Section: Discussionmentioning

confidence: 99%

Anticancer Activity of Acacia nilotica (L.) Wild. Ex. Delile Subsp. indica Against Dalton's Ascitic Lymphoma Induced Solid and Ascitic Tumor Model

Sakthivel¹,

Kannan²,

Angeline³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Effect of Acacia nilotica Against Dalton's Ascitic Lymphoma ModelAsian Pacific J Cancer Prev, 13, 3989-3995 IntroductionOver the past decade, Cancer is the leading cause of death worldwide and it is characterized by uncontrolled growth and spread of abnormal cells. World Health Organization (WHO) reported that there are 7.6 million deaths in 2008 and it is estimated up to 13.1 million deaths in 2030 (Merel et al., 2012). Treatment of cancer varies according to each type, has been facing large number of problems. Several ways in the treatment of cancer have been developed. Currently cancer is treated using surgery, radiation, and chemotherapy which are associated with severe side effects (Garcia et al., 2001;Edy et al., 2012). Even a large number of tumors are scantily responsive to cancer therapeutic drugs and radiotherapy. Identification and development of natural products used for cancer prevention have attracted a lot of attention globally. Herbal extracts with their proven potential and less side effects in therapeutics has replaced the synthetically derived drugs in modern allopathic medication system (Sakthivel and Guruvayoorappan, 2012). Traditionally used large number of medicinal plants and plant products has become the potential source of antitumor agents. Traditional healers of different regions in India particularly Chhattisgarh used Acacia species for treatment of various cancer types of mouth, bone and skin (Kalaivani and Mathew, 2010

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“…γ-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) which were included in biochemical test, were also showed as prognostic factors (Saif et al, 2005;Koukourakis et al, 2006;Pompella et al, 2006;Franzini et al, 2008;Franzini et al, 2009;Xie et al, 2014). However, previous studies had several drawbacks.…”

Section: Prognostic Model Built On Blood-based Biomarkers In Patientsmentioning

confidence: 99%

Prognostic Model Built on Blood-based Biomarkers in Patients with Metastatic Colorectal Cancer

Jiang²,

Yin

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: We had previously showed that the neutrophil lymphocyte ratio (NLR), γ-glutamyl transpeptidase (GGT) and carcinoembryonic antigen (CEA) are prognostic factors for metastatic colorectal cancer (mCRC) patients. In this study we developed a prognostic model based on these three indices. Materials and Methods: A total of 243 patients who were initially diagnosed as mCRC between 2005 and 2010 in the Sun Yat-sen University Cancer Center were studied. The endpoint was overall survival (OS). Results: NLR>3, elevated GGT and elevated CEA were confirmed as independent risk factors which could predict poor prognosis. Patients could be divided into three groups according to the number of risk factors they had. Those with two or three were defined as the high risk group, individuals with one risk factor as the modest risk group and patients without risk factor as the low risk group. The OS values for these three groups were 16.2 months (2.80~68.8), 24.2 months (4.07~79.0), and 37.2 months (12.6~87.8), respectively (p<0.001). Conclusions: We developed a simple but useful model based on NLR, GGT and CEA to provide prognostic information to clinical practice in highly selected mCRC patients. Further prospective and multi-center studies are warranted to test our model.

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Expression of γ-glutamyltransferase in cancer cells and its significance in drug resistance

Cited by 257 publications

References 65 publications

Prospective study of the association of gamma‐glutamyltransferase with cancer incidence in women

Prospective study of the association of gamma‐glutamyltransferase with cancer incidence in women

Anticancer Activity of Acacia nilotica (L.) Wild. Ex. Delile Subsp. indica Against Dalton's Ascitic Lymphoma Induced Solid and Ascitic Tumor Model

Prognostic Model Built on Blood-based Biomarkers in Patients with Metastatic Colorectal Cancer

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