Dataset Information

(-)-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.

SUBMITTER: Chen Y

PROVIDER: S-EPMC5995859 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Chen Yuwen Y Li Wenhua W Zeng Zhongqiu Z Tang Yaxiong Y

Scientific reports 20180611 1

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 ...[more]

PMID: 29891980

Similar Datasets

Project description:BackgroundFailure of treatment with gemcitabine in most cholangiocarcinoma (CCA) patients is due to drug resistance. The therapeutic potential of natural plant secondary compounds with minimal toxicity, such as cannabidiol (CBD), is a promising line of investigation in gemcitabine-resistant CCA. We aim to investigate the effects of CBD on gemcitabine-resistant CCA (KKU-213BGemR) cells in vitro and in vivo.MaterialsIn vitro, cell proliferation, colony formation, apoptosis and cell cycle arrest were assessed using MTT assay, clonogenicity assay and flow cytometry. The effect of CBD on ROS production was evaluated using the DCFH-DA fluorescent probe. The mechanism exerted by CBD on ER stress-associated apoptosis was investigated by western blot analysis. A gemcitabine-resistant CCA xenograft model was also used and the expression of PCNA and CHOP were evaluated by immunohistochemical analysis.ResultsThe IC50 values of CBD for KKU-213BGemR cells ranged from 19.66 to 21.05 µM. For a non-cancerous immortalized fibroblast cell line, relevant values were 18.29 to 19.21 µM. CBD suppressed colony formation by KKU-213BGemR cells in a dose-dependent manner in the range of 10 to 30 µM. CBD at 30 µM significantly increased apoptosis at early (16.37%) (P = 0.0024) and late (1.8%) stages (P < 0.0001), for a total of 18.17% apoptosis (P = 0.0017), in part by increasing ROS production (P < 0.0001). Multiphase cell cycle arrest significantly increased at G0/G1 with CBD 10 and 20 µM (P = 0.004 and P = 0.017), and at G2/M with CBD 30 µM (P = 0.005). CBD treatment resulted in increased expression of ER stress-associated apoptosis proteins, including p-PERK, BiP, ATF4, CHOP, BAX, and cytochrome c. In xenografted mouse, CBD significantly suppressed tumors at 10 and 40 mg/kg·Bw (P = 0.0007 and P = 0.0278, respectively), which was supported by an increase in CHOP, but a decrease in PCNA expression in tumor tissues (P < 0.0001).ConclusionThe results suggest that CBD exhibits potent anti-cancer activity against gemcitabine-resistant CCA in vitro and in vivo, in part via ER stress-mediated mechanisms. These results indicate that clinical explorative use of CBD on gemcitabine-resistant CCA patients is warranted.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets