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

Autor: Wenhua Li, Yuwen Chen, Yaxiong Tang, Zhongqiu Zeng
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Scientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
ISSN: 2045-2322
DOI: 10.1038/s41598-018-27036-6
Popis: 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje