The forecast of anticancer targets of cryptotanshinone based on reverse pharmacophore-based screening technology

Chin J Nat Med. 2014 Jun;12(6):443-8. doi: 10.1016/S1875-5364(14)60069-8.

Abstract

Anticancer targets of cryptotanshinone were evaluated and rapidly forecasted with PharmMapper, a reverse pharmacophore-based screening platform, as well as drug target databases, including PDTD, DrugBank and TTD. The pathway analyses for the collection of anticancer targets screened were carried out based on the KEGG pathway database, followed by the forecast of potential pharmacological activities and pathways of the effects of cryptotanshinone, and verification of some of the targets screened using whole cell tests. The results showed that a total of eight targets with anticancer potential were screened, including MAP2K1, RARα, RXRα, PDK1, CHK1, AR, Ang-1 R, and Kif11. These targets are mainly related to four aspects of the cancer growth: the cell cycle, angiogenesis, apoptosis, and androgen receptor. The cell tests showed that cryptotanshinone can inhibit the viability of human hepatoma cells SMMC-7721, which is related to the reduction of expression of MAP2K1 mRNA. This method provides a strong clue for the study of the anticancer effects and mechanisms of action of cryptotanshinone in the future.

Keywords: Anticancer; Cryptotanshinone; Forecast of target; Human hepatoma cells; Pharmacophore; Reverse screening technology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Cycle
  • Cell Line, Tumor
  • Databases, Factual
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Humans
  • MAP Kinase Kinase 1 / metabolism
  • Neovascularization, Pathologic
  • Phenanthrenes / pharmacology*
  • Phenanthrenes / therapeutic use
  • Phytotherapy
  • RNA, Messenger / metabolism
  • Receptors, Androgen / metabolism
  • Salvia miltiorrhiza / chemistry*

Substances

  • AR protein, human
  • Antineoplastic Agents, Phytogenic
  • Drugs, Chinese Herbal
  • Phenanthrenes
  • RNA, Messenger
  • Receptors, Androgen
  • cryptotanshinone
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human