19-(Benzyloxy)-19-oxojolkinolide B (19-BJB), an ent-abietane diterpene diepoxide, inhibits the growth of bladder cancer T24 cells through DNA damage

PLoS One. 2021 Mar 16;16(3):e0248468. doi: 10.1371/journal.pone.0248468. eCollection 2021.

Abstract

Diterpenoids jolkinolide A and B, were first isolated from Euphorbia fischeriana. In our previous research, 19-(Benzyloxy)-19-oxojolkinolide B (19-BJB), a derivative of jolkinolides, was synthesized as a novel ent -abietane diterpene diepoxide. In this study, 19-BJB showed strong in vitro activity against bladder cancer cell lines. DNA damage which was observed through the interaction of 19-BJB with nucleotide chains and affected DNA repair resulted in the activation of checkpoint kinase 1 (Chk1) and checkpoint kinase 2 (Chk2) in bladder cancer cell lines. In vivo testing in nude mice also proved that 19-BJB revealed a potential inhibitory effect on tumor growth. Additionally, the 3D-QSAR models of jolkinolides were established. Briefly, we proved that 19-BJB could potentially be used as a drug to inhibit the growth of bladder tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / pharmacology*
  • Abietanes / therapeutic use
  • Animals
  • Antineoplastic Agents, Phytogenic
  • Cell Line, Tumor
  • Checkpoint Kinase 1 / metabolism
  • Checkpoint Kinase 2 / metabolism
  • DNA Damage / drug effects*
  • DNA Repair
  • Diterpenes / pharmacology*
  • Diterpenes / therapeutic use
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Euphorbia / chemistry
  • Humans
  • Male
  • Mice
  • Molecular Docking Simulation
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Abietanes
  • Antineoplastic Agents, Phytogenic
  • Diterpenes
  • Drugs, Chinese Herbal
  • Checkpoint Kinase 2
  • CHEK1 protein, human
  • CHEK2 protein, human
  • Checkpoint Kinase 1

Grants and funding

This research was funded by the National Natural Science Foundation of China (No. 30973607; No. 81172934); Ministry of Science and Technology of Taiwan (MOST 103-2911-I-002-303; MOST 104-2911-I-002-302; MOST 107-2320-B-037-001), National Health Research Institutes of Taiwan (NHRI-EX104-10241BI).