PLoS ONE (Jan 2021)

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

  • Ke Wang,
  • Juan-Cheng Yang,
  • Yeong-Jiunn Jang,
  • Guan-Yu Chen,
  • Ya-Jing Zhang,
  • Yun-Hao Dai,
  • Da-Yong Zhang,
  • Yang-Chang Wu

DOI
https://doi.org/10.1371/journal.pone.0248468
Journal volume & issue
Vol. 16, no. 3
p. e0248468

Abstract

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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.