Thapsigargin-From Traditional Medicine to Anticancer Drug

Int J Mol Sci. 2020 Dec 22;22(1):4. doi: 10.3390/ijms22010004.


A sesquiterpene lactone, thapsigargin, is a phytochemical found in the roots and fruits of Mediterranean plants from Thapsia L. species that have been used for centuries in folk medicine to treat rheumatic pain, lung diseases, and female infertility. More recently thapsigargin was found to be a potent cytotoxin that induces apoptosis by inhibiting the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) pump, which is necessary for cellular viability. This biological activity encouraged studies on the use of thapsigargin as a novel antineoplastic agent, which were, however, hampered due to high toxicity of this compound to normal cells. In this review, we summarized the recent knowledge on the biological activity and molecular mechanisms of thapsigargin action and advances in the synthesis of less-toxic thapsigargin derivatives that are being developed as novel anticancer drugs.

Keywords: anticancer activity; apoptosis; cytotoxin; mipsagargin; prodrug; prostate-specific antigen; prostate-specific membrane antigen; sarcoplasmic/endoplasmic reticulum Ca2+ ATPase; thapsigargin; unfold protein response.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Endoplasmic Reticulum Stress / drug effects
  • Humans
  • Medicine, Traditional / methods*
  • Molecular Structure
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Thapsia / chemistry*
  • Thapsigargin / chemistry
  • Thapsigargin / therapeutic use*
  • Unfolded Protein Response / drug effects


  • Antineoplastic Agents
  • Thapsigargin