Triptolide sensitizes breast cancer cells to Doxorubicin through the DNA damage response inhibition

Mol Carcinog. 2018 Jun;57(6):807-814. doi: 10.1002/mc.22795. Epub 2018 Mar 25.


Triptolide is an active component from a Chinese herb, Tripterygium wilfordii which has been applied for treating immune-related diseases over centuries. Recently, it was reported that a variety of cancer cell lines could be sensitized to DNA-damage based chemotherapy drugs in combination with Triptolide treatment. In the present study, we show that a short time exposure (3 h) to Triptolide, which did not trigger apoptosis, could specifically increase breast cancer cells sensitivity to Doxorubicin rather than other chemotherapy drugs including Paclitaxel, Fluorouracil, and Mitomycin C. Further studies revealed Triptolide downregulated ATM expression and inhibited DNA damage response to DNA double- strand breaks. Moreover, the chemosensitization effect to Doxorubicin from Triptolide was attenuated by overexpression of ATM in breast cancer cells. Our findings suggest that Triptolide specifically chemosensitizes breast cancer cells to Doxorubicin prior to apoptosis initiation through downregulating ATM expression and inhibiting DNA damage response.

Keywords: ATM; DNA damage response; Triptolide; chemosensitization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • DNA Breaks, Double-Stranded / drug effects*
  • DNA Damage*
  • Diterpenes / pharmacology*
  • Doxorubicin / pharmacology*
  • Epoxy Compounds / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MCF-7 Cells
  • Phenanthrenes / pharmacology*


  • Antineoplastic Agents
  • Diterpenes
  • Epoxy Compounds
  • Phenanthrenes
  • triptolide
  • Doxorubicin
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins