Targeting thapsigargin towards tumors

Steroids. 2015 May:97:2-7. doi: 10.1016/j.steroids.2014.07.009. Epub 2014 Jul 24.

Abstract

The skin irritating principle from Thapsia garganica was isolated, named thapsigargin and the structure elucidated. By inhibiting the sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) thapsigargin provokes apoptosis in almost all cells. By conjugating thapsigargin to peptides, which are only substrates for either prostate specific antigen (PSA) or prostate specific membrane antigen (PSMA) prodrugs were created, which selectively affect prostate cancer cells or neovascular tissue in tumors. One of the prodrug is currently tested in clinical phase II. The prodrug under clinical trial has been named mipsagargin.

Keywords: Prodrug; Prostate specific antigen (PSA); Prostate specific membrane antigen (PSMA); Sarco/endoplasmic reticulum (SERCA); Targeting drugs; Thapsigargin.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apiaceae / chemistry*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Male
  • Mice
  • Molecular Structure
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / pathology
  • Prodrugs / chemistry
  • Prodrugs / isolation & purification
  • Prodrugs / pharmacology*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / antagonists & inhibitors
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
  • Soft Tissue Neoplasms / drug therapy*
  • Soft Tissue Neoplasms / pathology
  • Thapsigargin / chemistry
  • Thapsigargin / isolation & purification
  • Thapsigargin / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Prodrugs
  • Thapsigargin
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases