Curcumin and liver cancer: a review Darvesh, Altaf S; Aggarwal, Bharat B; Bishayee, Anupam
Current pharmaceutical biotechnology
13, Številka:
1
Journal Article
Recenzirano
Primary liver cancer, also known as hepatocellular carcinoma (HCC), is one of the most lethal cancers having worldwide prevalence. Although most HCC cases are reported in the developing countries of ...Asia and Africa, there has been an alarming increase in HCC cases in Western Europe as well as United States. Chronic liver diseases, viral hepatitis, alcoholism as well as dietary carcinogens, such as aflatoxins and nitrosoamines, contribute to HCC. Liver transplantation as well as surgical resection at best offer limited treatment options. Thus, there exists a critical need to investigate and evaluate possible alternative chemopreventive and therapeutic strategies which may be effective in the control of liver cancer. HCC, most often, develops and progresses in a milieu of oxidative stress and inflammation. Phytochemicals, such as dietary polyphenols endowed with potent antioxidant as well as anti-inflammatory properties, provide a suitable alternative in affording alleviation of HCC. Curcumin, the principal polyphenolic curcuminoid, obtained from the turmeric rhizome Curcuma longa has long been used to cure several chronic ailments, such as neoplastic and neurodegenerative diseases. Studies suggest that curcumin may have antitumor, antioxidant, and anti-inflammatory properties. This article reviews the effects of curcumin in preclinical in vitro and in vivo models of HCC with particular emphasis to its antioxidant, apoptotic and anti-inflammatory effects as well as involvement in various molecular signaling mechanisms. This review also discusses potential challenges involved in the use of curcumin in HCC, such as bioavailability, pharmacokinetics, drug delivery as well as paucity of clinical studies.
The prophylactic and therapeutic properties of tea have been attributed to green tea catechins and black tea theaflavins besides several other polyphenolic compounds. Tea polyphenols possess potent ...antioxidant and antiinflammatory properties and modulate several signaling pathways. These biochemical facets of tea polyphenols are responsible for its anticancer properties. Several lethal cancers, such as liver cancer, develop within a background of oxidative stress and inflammation. Liver cancer, also known as hepatocellular carcinoma (HCC), has been shown to occur throughout the world including Asia, Africa, Western Europe, and the United States. Phytochemicals, such as tea polyphenols, provide an effective and promising alternative for the chemoprevention and treatment of HCC. In this article, we systematically review, for the first time, the effects of tea polyphenols in the preclinical in vitro and in vivo HCC models. The review also examines, in critical detail, the biochemical mechanisms involved in the chemopreventive and antineoplastic effects of tea polyphenols in hepatic cancer. Finally, we highlight the role of synergy, bioavailability and pharmacokinetics of tea polyphenols, current status of clinical trials, discuss future directions, and comment on the future challenges involved in the effective use of tea polyphenols for the prevention and management of liver cancer.
Summary Hepatocellular carcinoma (HCC) is one of the most common cancers and lethal diseases in the world. Although the majority of HCC cases occur in developing countries of Asia and Africa, the ...prevalence of liver cancer has risen considerably in Japan, Western Europe as well as the United States. HCC most commonly develops in patients with chronic liver disease, the etiology of which includes viral hepatitis (B and C), alcohol, obesity, iron overload and dietary carcinogens, including aflatoxins and nitrosamines. The current treatment modalities, including surgical resection and liver transplantation, have been found to be mostly ineffective. Hence, there is an obvious critical need to develop alternative strategies for the chemoprevention and treatment of HCC. Oxidative stress as well as inflammation has been implicated in the development and progression of hepatic neoplasia. Using naturally occurring phytochemicals and dietary compounds endowed with potent antioxidant and antiinflammatory properties is a novel approach to prevent and control HCC. One such compound, resveratrol, present in grapes, berries, peanuts as well as red wine, has emerged as a promising molecule that inhibits carcinogenesis with a pleiotropic mode of action. This review examines the current knowledge on mechanism-based in vitro and in vivo studies on the chemopreventive and chemotherapeutic potential of resveratrol in liver cancer. Pre-clinical and clinical toxicity studies as well as pharmacokinetic data of resveratrol have also been highlighted in this review. Future directions and challenges involved in the use of resveratrol for the prevention and treatment of HCC are also discussed.
Hepatocellular carcinoma (HCC) remains one of the most lethal cancers in the world. Since current treatment options including surgical resection and liver transplantation offer limited therapeutic ...benefits, there exists a need to evaluate novel therapeutic strategies for the amelioration of HCC. Hepatic tumors are highly vascularized, possessing a rich network of blood vessels and capillaries and there exist an angiogenic component to the tumor growth observed in HCC. Thus, anti-angiogenic therapy has been suggested to possess tremendous therapeutic potential in the treatment of HCC. The process of angiogenesis involves multiple biochemical checkpoints and signaling steps, and thus providing a multitude of opportunities for therapeutic intervention. In this review, we highlight the role of angiogenesis and its use as a therapeutic strategy for HCC. The first part of the article reviews the angiogenic mechanisms with particular emphasis on the multitude of biochemical factors, such as receptors, enzymes and cytokines involved in the complex interplay of new capillary growth. Next, we present the pre-clinical studies which elucidate the anti-angiogenic effects of both dietary and non-dietary agents in animal models of HCC. Of particular interest is the examination of the effects of the antiangiogenic agents on the various angiogenic markers in the hepatic tissue of the animal challenged either with a hepatocarcinogen or xenografted with hepatic neoplastic cells. The review also highlights the clinical investigations carried out in HCC patients to evaluate the therapeutic potential of pharmacological agents with proven anti-angiogenic properties. Finally, the future directions as well as the benefits and potential challenges involved in the use of antiangiogenic pharmacotherapy in the treatment of HCC are also discussed.
•Lipoprotein lipase plays a key part in human triglyceride metabolism.•Certain liver-derived proteins stimulate or inhibit LPL activity.•Novel small-molecule and gene therapy approaches directly ...stimulate LPL activity.•Antisense oligos, antibodies and siRNA against anti-LPL proteins stimulate LPL.
Although statins and other pharmacological approaches have improved the management of lipid abnormalities, there exists a need for newer treatment modalities especially for the management of hypertriglyceridemia. Lipoprotein lipase (LPL), by promoting hydrolytic cleavage of the triglyceride core of lipoproteins, is a crucial node in the management of plasma lipid levels. Although LPL expression and activity modulation is observed as a pleiotropic action of some the commonly used lipid lowering drugs, the deliberate development of drugs targeting LPL has not occurred yet. In this review, we present the biology of LPL, highlight the LPL modulation property of currently used drugs and review the novel emerging approaches to target LPL.
Can modulating the levels of LPL regulatory proteins be a viable strategy to lower plasma lipids and attenuate metabolic diseases?
The present research is a comparative study that reports an economical and accessible method to synthesize niobium (Nb) and Tantalum (Ta) selenides and tellurides with useful application in the ...removal of pollutants in textile, paper, and dyeing industries as well as in medical field. In this study, solid-state process was used to generate nanocomposites and various characterization techniques were employed to compare two groups of materials under investigation. Structure, morphology, elemental constitution, and functional groups of synthesized materials were analyzed with XRD, FESEM coupled with EDS, FTIR, and Raman spectroscopy, respectively. HR-TEM images displayed nanoscale particles with tetragonal and monoclinic crystal structures. The optical properties were evaluated in terms of cut-off wavelength and optical band gap using UV-visible spectroscopy. A comparative behavior of both groups of compounds was assessed with regards to their catalytic and microcidal properties. Extracted nanocomposites when used as catalysts, though isomorphs of each other, showed markedly different behavior in catalytic degradation of MB dye in the presence of NaBH
4
that was employed as a reducing agent. This peculiar deviation might be attributed to slight structural differences between them.
Escherichia coli
and
Staphylococcus aureus
(G –ve and + ve bacteria, respectively) were designated as model strains for in vitro antibacterial tests of both clusters by employing disk diffusion method. Superior antibacterial efficacy was observed for telluride system (significant inhibition zones of 26-35 mm) compared with selenide system (diameter of inhibition zone ranged from 0.8 mm to 1.9 mm). In addition, molecular docking study was undertaken to ascertain the binding interaction pattern between NPs and active sites in targeted cell protein. The findings were in agreement with antimicrobial test results suggesting NbTe
4
to be the best inhibitor against FabH and FabI enzymes.
Twenty-eight genetic loci are associated with serum urate levels in Europeans. Evidence for association with gout at most loci is absent, equivocal or not replicated. Our aim was to test the loci for ...association with gout meeting the American College of Rheumatology gout classification criteria in New Zealand European and Polynesian case-control sample sets.
648 European cases and 1550 controls, and 888 Polynesian (Ma¯ori and Pacific) cases and 1095 controls were genotyped. Association with gout was tested by logistic regression adjusting for age and sex. Power was adequate (>0.7) to detect effects of OR>1.3.
We focused on 24 loci without previous consistent evidence for association with gout. In Europeans, we detected association at seven loci, one of which was the first report of association with gout (IGF1R). In Polynesian, association was detected at three loci. Meta-analysis revealed association at eight loci-two had not previously been associated with gout (PDZK1 and MAF). In participants with higher Polynesian ancestry, there was association in an opposing direction to Europeans at PRKAG2 and HLF (HLF is the first report of association with gout). There was obvious inconsistency of gout association at four loci (GCKR, INHBC, SLC22A11, SLC16A9) that display very similar effects on urate levels.
We provide the first evidence for association with gout at four loci (IGF1R, PDZK1, MAF, HLF). Understanding why there is lack of correlation between urate and gout effect sizes will be important in understanding the aetiology of gout.
Alzheimer's disease (AD) and its related dementia has shown an alarming rise in the global population. Although considerable efforts have been made to develop effective therapeutic agents for AD ...therapy, drug development has not met significant clinical success. Current pharmacotherapy of AD is limited to cholinesterase inhibitors and the N-methyl-D-aspartate antagonist memantine. Considerable research is underway to develop newer agents for the management of AD. Since amyloid-β (Aβ) has been implicated in AD pathogenesis, the use of β secretase inhibitors as well as immunotherapy against Aβ has been investigated. A considerable effort has been spent investigating the therapeutic potential of antioxidants and anti-inflammatory agents, several of natural products and dietary origin, in AD treatment. Numerous drug targets have also been investigated for AD treatment and a modest drug pipeline is available. Despite these efforts, drug development for AD has proved extremely difficult and most clinical trials have afforded disappointing results.
Anthocyanins are known to possess potent anticarcinogenic properties against several cancers thus demonstrating potential for cancer prevention. Black currant (Ribes nigrum L., Grossulariaceae) ...fruits have a high anthocyanin content. This “superfruit” is known to possess various pharmacological effects including alleviation of chronic oxidative stress and inflammation. In contrast to a large volume of literature on the health benefits of black currant, limited evidence on antitumor effects of black currant exists with virtually no data on the prevention of experimental carcinogenesis. In the current study, we have investigated the chemopreventive effects of an anthocyanin-rich black currant skin extract (BCSE) utilizing our well-characterized model of rat liver carcinogenesis. Initiation of hepatocarcinogenesis was done by intraperitoneal injection of diethylnitrosamine (DENA) followed by promotion with phenobarbital. The rats were exposed to dietary BCSE for 4 weeks prior to initiation, and the treatment was continued for 22 consecutive weeks. BCSE dose-dependently decreased the incidence, total number, multiplicity, size and volume of preneoplastic hepatic nodules. The antihepatocarcinogenic effect of BCSE was confirmed by histopathological examination of liver sections. Immunohistochemical analysis of proliferating cell nuclear antigen and DNA fragmentation revealed BCSE-mediated inhibition of abnormal cell proliferation and induction of apoptosis in DENA-induced rat liver tumorigenesis respectively. Mechanistic studies revealed that BCSE-mediated proapototic signal during experimental hepatocarcinogenesis may be propagated via the up-regulation of Bax and down-regulation of Bcl-2 expression at the translational level. These results along with a safety profile of BCSE encourage the development of black currant bioactive constituents as chemopreventive agents for human liver cancer.
Hepatocellular carcinoma (HCC), considered to be one of the most lethal cancers with almost > 1 million deaths reported annually worldwide, remains a devastating disease with no known effective cure. ...Hence, chemopreventive strategies come into play, offering an effective and safe mode of treatment, ideal to ward off potential cancer risks and mortality. A major predisposing condition, pertinent to the development and progression of HCC is oxidative stress. We previously reported a striking chemopreventive effect of anthocyanin-rich black currant skin extract (BCSE) against diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats. The current study aims to elucidate the underlying antioxidant mechanisms of black currant anthocyanins implicated in the previously observed chemopreventive effects against experimental hepatocarcinogenesis. Dietary BCSE (100 and 500 mg/kg) administered four weeks before and 18 weeks after DENA challenge decreased abnormal lipid peroxidation, protein oxidation, and expression of inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT) in a dose-responsive fashion. Mechanistic studies revealed that BCSE upregulated the gene expression of a number of hepatic antioxidant and carcinogen detoxifying enzymes, such as NAD(P)H:quinone oxidoreductase, glutathione S-transferase, and uridine diphosphate-glucuronosyltransferase isoenzymes, in DENA-initiated animals. Protein and mRNA expressions of nuclear factor E2-related factor 2 (Nrf2) were substantially elevated with BCSE treatment, providing a direct evidence of a coordinated activation of the Nrf2-regulated antioxidant pathway, which led to the upregulation of a variety of housekeeping genes. The results of our study provide substantial evidence that black currant bioactive anthocyanins exert chemopreventive actions against DENA-inflicted hepatocarcinogenesis by attenuating oxidative stress through activation of Nrf2 signaling pathway.
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