Trans-(±)-TTPG-B Attenuates Cell Cycle Progression and Inhibits Cell Proliferation on Cholangiocarcinoma Cells
Issued Date
2023-11-01
Resource Type
eISSN
14203049
Scopus ID
2-s2.0-85176459841
Journal Title
Molecules
Volume
28
Issue
21
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecules Vol.28 No.21 (2023)
Suggested Citation
Rattanaburee T., Chompunud Na Ayudhya C., Thongpanchang T., Tipmanee V., Graidist P. Trans-(±)-TTPG-B Attenuates Cell Cycle Progression and Inhibits Cell Proliferation on Cholangiocarcinoma Cells. Molecules Vol.28 No.21 (2023). doi:10.3390/molecules28217342 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/91124
Title
Trans-(±)-TTPG-B Attenuates Cell Cycle Progression and Inhibits Cell Proliferation on Cholangiocarcinoma Cells
Author's Affiliation
Other Contributor(s)
Abstract
This research aimed to determine the target protein and molecular mechanism of trans-(±)-kusunokinin ((±)-KU) derivatives (trans-(±)-ARC and trans-(±)-TTPG-B). Molecular docking was used to predict potential synthesized (±)-KU targets among 22 proteins. The (±)-TTPG-B bound HSP90α better than EC44, native (±)-KU and (-)-KU, and (±)-KU and (−)-ARC. In contrast, (−)-ARC bound PI3K more strongly than any other test compound. CSF1R and AKR1B1 were not supposed to be the target of (±)-TTPG-B and (±)-ARC, unlike native (±)-KU. The (±)-TTPG-B bound Tyr139 and Trp162 of HSP90α. Moreover, (−)-ARC bound PI3K via hydrogen bonds and π-π stacking at distinct amino acids, which was different from the other tested compounds. Using half of the IC50 concentration, (±)-TTPG-B, (±)-KU and (±)-ARC enhanced cell cycle arrest at the G0/G1 phase after 12 h and 24 h on KKU-M213 (CCA) cells. The (±)-TTPG-B showed a stronger inhibitory effect than (±)-ARC and (±)-KU on HSP90α, PI3K, HSP90β, c-Myc, AKT, MEK1, CyclinB1, CyclinD1, and CDK1 for 24 and 48 h after treatment with the same concentration (0.015 µM). Thus, trans-(±)-TTPG-B, a newly synthesized compound, has pharmacological potential for development as a target therapy for CCA treatment.