Curcumin and liver cancer: a review.
Humans; Animals; Anticarcinogenic Agents/*therapeutic use; Antioxidants/therapeutic use; Anti-Inflammatory Agents/therapeutic use; Curcumin/*therapeutic use; Liver Neoplasms/*drug therapy/prevention & control; Carcinoma; Antineoplastic Agents; Hepatocellular/*drug therapy/prevention & control; Phytogenic/*therapeutic use
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.
Darvesh Altaf S; Aggarwal Bharat B; Bishayee Anupam
Current pharmaceutical biotechnology
2012
2012-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.2174/138920112798868791" target="_blank" rel="noreferrer noopener">10.2174/138920112798868791</a>
Natural products of dietary origin as lead compounds in virtual screening and drug design.
Humans; Animals; Diet; Resveratrol; *Drug Design; *Biological Products/pharmacology; Caffeine/pharmacology; Curcumin/pharmacology; Genistein/pharmacology; Stilbenes/pharmacology
Natural products have been found to be useful in the treatment of several diseases across the ages. In this article, we review the use of natural products, obtained from dietary sources, as lead compounds in developing novel therapeutic agents. These compounds have shown tremendous promise in the prevention and as well as treatment of a variety of chronic ailments. In addition, to being patentable and biocompatible, these compounds are a rich source of novel scaffolds to invigorate the pipelines of the pharmaceutical industry. In this communication, we also focus on studies which show how natural products have proved useful as lead compounds in virtual screening and structure-based drug design programs. Natural dietary constituents, such as resveratrol, curcumin and caffeine as well as other compounds, are discussed to illustrate this approach.
Geldenhuys Werner J; Bishayee Anupam; Darvesh Altaf S; Carroll Richard T
Current pharmaceutical biotechnology
2012
2012-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.2174/138920112798868548" target="_blank" rel="noreferrer noopener">10.2174/138920112798868548</a>
Alteration of hepatic proinflammatory cytokines is involved in the resveratrol-mediated chemoprevention of chemically-induced hepatocarcinogenesis.
Female; Animals; Rats; Gene Expression Regulation/drug effects; Liver/drug effects/metabolism; Resveratrol; Diethylnitrosamine; Anticarcinogenic Agents/pharmacology/*therapeutic use; Cytokines/genetics/*metabolism; Phenobarbital; Stilbenes/pharmacology/*therapeutic use; Sprague-Dawley; RNA; Messenger/metabolism; Liver Neoplasms; Experimental/chemically induced/metabolism/*prevention & control
Hepatocellular carcinoma (HCC), one of the most common cancers in the world, is a leading cause of cancerrelated mortality. HCC develops most frequently in the background of oxidative stress and chronic hepatic inflammation due to viral infections, alcohol abuse as well as exposure to environmental and dietary carcinogens. As the prognosis of HCC is extremely poor and mostly unresponsive to current chemotherapeutic treatment regimens, novel preventive approaches like chemoprevention are urgently needed. We have recently found that resveratrol, a dietary polyphenol present in grapes, berries, peanuts as well as red wine, prevents diethylnitrosamine (DENA)-initiated hepatocarcinogenesis in rats through suppression of inflammation and oxidative stress. As cytokines are considered to be important mediators of inflammation, the objective of the present study was to investigate the effects of resveratrol on hepatic cytokines during DENA-initiated hepatocarcinogenesis in rats. Liver samples were harvested from our previous study in which resveratrol (50, 100 and 300 mg/kg) was found to exert a chemopreventive action against rat liver tumorigenesis induced by DENA. The levels of proinflammatory cytokines, namely tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin- 6 (IL-6), were measured using enzyme-linked immunosorbent assays. The mRNA expression of these cytokines was studied by reverse transcriptase-polymerase chain reaction for comparison. Resveratrol treatment reversed the DENAinduced alteration of the level and expression of hepatic TNF-alpha, IL-1beta and IL-6. From the current results in conjunction with our previous findings, it can be concluded that resveratrol-mediated chemoprevention of rat liver carcinogenesis is related to alteration of proinflammatory cytokines.
Mbimba Thomas; Awale Prabha; Bhatia Deepak; Geldenhuys Werner J; Darvesh Altaf S; Carroll Richard T; Bishayee Anupam
Current pharmaceutical biotechnology
2012
2012-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.2174/138920112798868575" target="_blank" rel="noreferrer noopener">10.2174/138920112798868575</a>