1. 19-(Benzyloxy)-19-oxojolkinolide B (19-BJB), an ent-abietane diterpene diepoxide, inhibits the growth of bladder cancer T24 cells through DNA damage.
- Author
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Wang K, Yang JC, Jang YJ, Chen GY, Zhang YJ, Dai YH, Zhang DY, and Wu YC
- Subjects
- Abietanes therapeutic use, Animals, Antineoplastic Agents, Phytogenic, Cell Line, Tumor, Checkpoint Kinase 1 metabolism, Checkpoint Kinase 2 metabolism, DNA Repair, Diterpenes therapeutic use, Drugs, Chinese Herbal therapeutic use, Euphorbia chemistry, Humans, Male, Mice, Molecular Docking Simulation, Urinary Bladder Neoplasms pathology, Xenograft Model Antitumor Assays, Abietanes pharmacology, DNA Damage drug effects, Diterpenes pharmacology, Drugs, Chinese Herbal pharmacology, Urinary Bladder Neoplasms drug therapy
- 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., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
- Published
- 2021
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