Evaluation of the medicinal herb Graptopetalum paraguayense as a treatment for liver cancer

PLoS One. 2015 Apr 7;10(4):e0121298. doi: 10.1371/journal.pone.0121298. eCollection 2015.

Abstract

Background: Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third most common cause of cancer-related death worldwide. Sorafenib is the only drug for patients with advanced-stage hepatocellular carcinoma (HCC) that has been shown to confer a survival benefit to patients with HCC; however, it has many side effects. Thus, alternate therapeutic strategies with improved safety and therapeutic efficacy for the management of HCC should be developed.

Methods and findings: We demonstrate that an extract of Graptopetalum paraguayense (GP) down-regulated the expression levels of several onco-proteins, including AURKA, AURKB, and FLJ10540, in HCC cells. To isolate the active components in the GP extracts, we prepared extracts fractions and assessed their effects on the expression of onco-proteins in HCC cells. The fraction designated HH-F3 was enriched in active ingredients, exhibited cytotoxic effects, and suppressed the expression of the onco-proteins in HCC cells. The structure of the main active compound in HH-F3 was found to be similar to that of the proanthocyanidin compounds derived from Rhodiola rosea. In addition, a distinct new compound rich in 3, 4, 5-trihydroxy benzylic moieties was identified in the HH-F3 preparations. Mechanistic studies indicated that HH-F3 induced apoptosis in HCC cells by promoting the loss of mitochondrial membrane potential and the production of reactive oxygen species. HH-F3 also enhanced PTEN expression and decreased AKT phosphorylation at Ser473 in a concentration-dependent manner in HCC cells. Moreover combination of GP or HH-F3 and sorafenib synergistically inhibits the proliferation of Huh7 cells. The treatment of a rat model with diethylnitrosamine (DEN)-induced liver cancer with extracts of GP and HH-F3 decreased hepatic collagen contents and inhibited tumor growth.

Conclusions: These results indicate that GP extracts and HH-F3 can protect the liver by suppressing tumor growth; consequently, these compounds could be considered for the treatment of HCC.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Male
  • Neoplasm Proteins / biosynthesis
  • Neoplasms, Experimental* / drug therapy
  • Neoplasms, Experimental* / metabolism
  • Neoplasms, Experimental* / pathology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plants, Medicinal / chemistry*
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Saxifragaceae / chemistry*

Substances

  • Neoplasm Proteins
  • Plant Extracts
  • Reactive Oxygen Species

Grant support

This work was supported by the Taiwan National Science Council under grant numbers NSC102-2627-B-010-001-, MOST103-2627-B-010-001-, and MOST103-2627-B-030-001-; the Taiwan Ministry of Economic Affairs grant numbers 99-EC-17-A-S1-152, 100-EC-17-A-S1-152, and 101-EC-17-A-S1-152); and by a grant from the Ministry of Education, Aim for the Top University Plan (103AC-T503). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.