Triptolide sensitizes liver cancer cell lines to chemotherapy in vitro and in vivo

Panminerva Med. 2014 Sep;56(3):211-20. Epub 2013 Dec 18.

Abstract

Aim: Triptolide is a diterpenoid epoxide isolated from the herb Tripterygium wilfordii, which has long been used as a natural medicine in China for many diseases including cancer. However, its effect on liver cancer has not yet been evaluated. The aim of this study is to investigate the effect of triptolide on liver cancer cell lines.

Methods: The effect of triptolide with cancer chemotherapeutics such as cisplatin and fluorouracil (5-FU) in vitro and in vivo on liver cancer cells has been investigated. Cell viability and protein expression were determined by MTT assay and Western blotting respectively. Apoptosis and reactive oxygen species (ROS) were detected by flow cytometry. The antitumor effects of triptolide alone or in combination were also measured in transplantation tumor models.

Results: The combination of triptolide plus chemotherapeutics (Cisplatin, 5-FU) reduced cancer cell viability and enhanced apoptosis compared with single treatment in vitro. Furthermore, cells treated with triptolide plus chemotherapeutics exhibited marked production of intracellular ROS and caspase-3 activity compared with single treatment, which paralleled the incidence of apoptosis. Triptolide and chemotherapeutics treatment also induced Bax expression, and inhibited Bcl-2 expression. Triptolide also boosted the anticancerous effects of cisplatin and 5-FU in nude mice compared with cisplatin or 5-FU alone treated tumors.

Conclusion: Our study demonstrated that triptolide is associated with increased cellular sensitivity of liver cancer cells to cisplatin and 5-FU in vivo and in vitro, and may provide new liver cancer treatment strategies.

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / chemistry
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Apoptosis
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Survival
  • Diterpenes / administration & dosage*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Drugs, Chinese Herbal / administration & dosage
  • Epoxy Compounds / administration & dosage
  • Female
  • Flow Cytometry
  • Fluorouracil / chemistry
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Mice
  • Mice, Nude
  • Oxidative Stress
  • Phenanthrenes / administration & dosage*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Tripterygium / chemistry
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents, Alkylating
  • BAX protein, human
  • Diterpenes
  • Drugs, Chinese Herbal
  • Epoxy Compounds
  • Phenanthrenes
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • triptolide
  • Caspase 3
  • Fluorouracil