title: Chinese herbal medicine-derived compounds for cancer therapy: a focus on hepatocellular carcinoma.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) as the major histological subtype of primary liver cancer remains one of the most common malignancies worldwide. Due to the complicated 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 anti-HCC compounds derived from CHM, especially their underlying pharmacological mechanisms.
  
  
  METHODS
  A systematic search of anti-HCC compounds from CHM was carried out focusing on literatures published both in English (PubMed, Scopus, Web of Science and Medline) and in Chinese academic databases (Wanfang and CNKI database).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Hu
authors.forename: Shengpeng
authors.initials: S
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Wu
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhang
authors.forename: Ruie
authors.initials: R
authors.lastname: Chen
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
authors.forename: Yitao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002681:China; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000302:isolation & purification / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008516:Medicine, Chinese Traditional
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal
keywords: AP-1; ARNT; ATP synthase H(+) transporting mitochondrial Fo complex-subunit B1; ATP5F1; Akt; CAV1; CDKs; CHM; COX-2; Cancer therapy; Chinese herbal medicine; Curcumin; ELAM-1; ERK1/2; HBV; HCC; HCV; HIF-1α; Hepatocellular carcinoma; ICAM-1; IL; JNK; MAPK; MMP; PARP; PCNA; PTEN; ROS; STAT; TCM; UDP-glucuronosyl transferase; UGT; VCAM-1; VEGF; activator protein 1; aryl hydrocarbon receptor nuclear translocate; c-Jun N-terminal kinases; caveolin-1; cyclin dependent protein kinases; cyclooxygenase-2; endothelial leukocyte adhesion molecule; extracellular regulated protein kinases 1/2; hepatitis B virus; hepatitis C virus; hepatocellular carcinoma; hypoxia-inducible factor-alpha; interleukin; intracellular adhesion molecule; matrix metalloproteinases; mitogen-activated protein kinases; phosphatase and tensin homolog; poly ADP-ribose polymerase; proliferating cell nuclear antigen; protein kinase B; reactive oxygen species; signal transducers and activators of transcription; traditional Chinese medicine; vascular cell adhesion molecule; vascular endothelial growth factor.