(-)-Gochnatiolide B, synthesized from dehydrocostuslactone, exhibits potent anti-bladder cancer activity in vitro and in vivo.

Abstract:

:With limited success achieved in bladder cancer patient management, novel agents are in urgent need for the purpose of therapy and prevention. As a sesquiterpenoid dimmer isolated from Gochnatia pomculat, (-)-gochnatiolide B has been bio-mimetically synthesized in multiple steps with a poor yield, which heavily limited the further research and clinical application. Herein, (-)-gochnatiolide B was synthesized beginning with dehydrocostuslactone in four steps with a total yield of 26%. MTT assays showed that (-)-gochnatiolide B inhibited the growth of vast majority of human cancer cells especially bladder cancer cells. Mechanistically, (-)-gochnatiolide B induced the increased expression of pro-apoptotic proteins and the decreased expression of anti-apoptosis proteins and further resulted in apoptosis of T24 cells. (-)-Gochnatiolide B induced G1 arrest which associated with SKP2 downregulation, leading to p27/Kip1 accumulation and downregulation of cyclin D1 in T24 cells. Furthermore, in vivo studies showed that (-)-gochnatiolide B remarkably inhibited tumor growth by 81% compared with vehicle control. Taken together, (-)-gochnatiolide B exhibits inhibitory activity against bladder cancer cells both in vitro and in vivo by inducing apoptosis, which suggests that (-)-gochnatiolide B could be an important candidate compound for prevention and treatment of bladder cancer.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Chen Y,Li W,Zeng Z,Tang Y

doi

10.1038/s41598-018-27036-6

subject

Has Abstract

pub_date

2018-06-11 00:00:00

pages

8807

issue

1

issn

2045-2322

pii

10.1038/s41598-018-27036-6

journal_volume

8

pub_type

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