Chinese herbal medicine-derived compounds for cancer therapy: A focus on hepatocellular carcinoma
ABSTRACT Hepatocellular carcinoma (HCC) as the major histological subtype of primary liver cancer remains one of the most common malignancies worldwide. Due to quite complicated the molecular pathogenesis of HCC, the option for effective systemic treatment is quite limited. There exists a critical need to explore and evaluate possible alternative strategies for effective control of HCC. With a long history of clinical use, Chinese herbal medicine (CHM) is emerging as a noticeable choice for its multi-level, multi-target and coordinated intervention effects against HCC. With the aids of phytochemistry and molecular biological approaches, in the past decades many CHM-derived compounds have been carefully studied through both preclinical and clinical researches and have shown great potential in novel anti-HCC natural product development. The present review aimed at providing the most recent developments on CHM-derived anti-HCC compounds, especially their underlying pharmacological mechanisms.
A systematic search of CHM-derived anti-HCC compounds was carried out focusing on literatures published both in English (PubMed, Scopus, Web of Science and Medline) and in Chinese academic database (Wanfang and CNKI database).
In this review, we tried to give a timely and comprehensive update about the anti-HCC effects and targets of several representative CHM-derived compounds, namely curcumin, resveratrol, silibinin, berberine, quercetin, tanshinone II-A and celastrol. Their mechanisms of anti-HCC behaviors, potential side effects or toxicity and future research directions were discussed.
Herbal compounds derived from CHM are of much significance in devising new drugs and providing unique ideas for the war against HCC. We propose that these breakthrough findings may have important implications for targeted-HCC therapy and modernization of CHM.
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ABSTRACT: Protein homeostatic regulators have been shown to ameliorate single, loss-of-function protein diseases but not to treat broader animal disease models that may involve cell death. Diseases often trigger protein homeostatic instability that disrupts the delicate balance of normal cellular viability. Furthermore, protein homeostatic regulators have been delivered invasively and not with simple oral administration. Here, we report the potent homeostatic abilities of celastrol to promote cell survival, decrease inflammation, and maintain cellular homeostasis in three different disease models of apoptosis and inflammation involving hepatocytes and cardiomyocytes. We show that celastrol significantly recovers the left ventricular function and myocardial remodeling following models of acute myocardial infarction and doxorubicin-induced cardiomyopathy by diminishing infarct size, apoptosis, and inflammation. Celastrol prevents acute liver dysfunction and promotes hepatocyte survival after toxic doses of thioacetamide. Finally, we show that heat shock response (HSR) is necessary and sufficient for the recovery abilities of celastrol. Our observations may have dramatic clinical implications to ameliorate entire disease processes even after cellular injury initiation by using an orally delivered HSR activator.Cell Stress and Chaperones 10/2014; DOI:10.1007/s12192-014-0536-1 · 2.54 Impact Factor
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ABSTRACT: The blessed milk thistle (Silybum marianum L.), a flowering plant native to Mediterranean Europe, has been consumed and extensively used as a cure for various chronic liver ailments over several centuries. Milk thistle extract, known as silymarin, is a complex mixture of seven major flavonolignans and one flavonoid. The phytoconstituents of silymarin owe their therapeutic and hepatoprotective effects to their strong antioxidant and anti-inflammatory properties. Primary liver cancer, also known as hepatocellular carcinoma (HCC), occurs in a milieu of oxidative stress and inflammation. The etiology of HCC includes chronic infection with hepatitis B and C viruses, cirrhosis, and exposure to dietary and environmental hepatocarcinogens. Current therapeutic options for HCC, including surgical resection and liver transplantation, have limited benefits and are essentially ineffective. Chemoprevention, using phytochemicals with potent antioxidant and anti-inflammatory properties, represents a fascinating strategy, which has been a subject of intense investigation in the recent years. In this review, we explore the potential role of silymarin as a chemopreventive and therapeutic agent for HCC. The review systematically evaluates the preclinical in-vitro and in-vivo studies investigating the effects of silymarin and its constituents on HCC. The biochemical mechanisms involved in the anti-liver-cancer effects of silymarin have been presented. The current status of clinical studies evaluating the potential of role of silymarin in liver cancer, especially that caused by hepatitis C virus, has also been examined. Potential challenges and future directions of research involved in the 'bench-to-bedside' transition of silymarin phytoconstituents for the chemoprevention and treatment of HCC have also been discussed.Anti-Cancer Drugs 01/2015; 26(5). DOI:10.1097/CAD.0000000000000211 · 1.89 Impact Factor
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ABSTRACT: Tanshinone IIA (Tan IIA) is one of the main natural active ingredients purified from Salvia miltiorrhiza radix, which has long been used in clinical practice in China to treat diseases including liver fibrosis, Alzheimer's disease, and cardiovascular diseases. Tan IIA has hepatoprotective properties, and is an efficacious PXR agonist. Our study was designed to observe the function and mechanism of the hepatoprotective properties of Tan IIA. HepG2 cells were used to investigate the vitrol effects of Tan IIA on PXR and CP3A4. Gut-formed LCA is hepatotoxic, and has been implicated in the pathogenesis of cholestatic diseases. To further investigate the hepatoprotective mechanisms of Tan IIA against LCA-induced cholestasis in vivo, we choose the normal mice and siRNA-treated mice. The in vitro study demonstrated that the effect of Tan IIA on CYP3A4 was mediated by transactivation of PXR in a dose- and time-dependent manner. The in vivo experiments using PXR siRNA revealed that Tan IIA could protect against LCA-induced hepatotoxicity and cholestasis in a dose-dependent manner. These effects were partially caused by the upregulation of PXR, as well as Cyp3a11, Cyp3a13, and Mdr1, which are the enzymes responsible for LCA metabolism. This is the first report showing that the hepatoprotective effects of Tan IIA are partly mediated by PXR. Copyright © 2015. Published by Elsevier Ireland Ltd.Journal of Ethnopharmacology 02/2015; 164. DOI:10.1016/j.jep.2015.01.047 · 2.94 Impact Factor