Probing the Anti-Cancer Potency of Sulfated Galactans on Cholangiocarcinoma Cells Using Synchrotron FTIR Microspectroscopy, Molecular Docking, and In Vitro Studies

Marine Drugs

Tawut Rudtanatip¹  Thanvarin Thitiphatphuvanon²  Kittiya Supradit³  Boonyakorn Boonsri³  Kanokpan Wongprasert³  Apinya Sayinta³  Jinchutha Duangdara³  Kiattawee Choowongkomon⁴  Buabarn Kuaprasert⁵ 

[1] Department of Anatomy, Faculty of Medicine, Khon Kean University, Khon Kean 40002, Thailand;Department of Anatomy, Faculty of Medicine, Siam University, Bangkok 10160, Thailand;Department of Anatomy, Faculty of Science, Mahidol University, Bangkok 10400, Thailand;Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand;Research and Facility Division, Synchrotron Light Research Institute (Public Organization), Nakhorn Ratchasima 30000, Thailand;

关键词: red alga Gracilaria fisheri;    sulfated galactans;    synchrotron-FTIR-MS;    molecular docking;    epidermal growth factor receptor;    anti-cancer;   

DOI  :  10.3390/md19050258

来源: DOAJ

【 摘 要 】

Sulfated galactans (SG) isolated from red alga Gracilaria fisheri have been reported to inhibit the growth of cholangiocarcinoma (CCA) cells, which was similar to the epidermal growth factor receptor (EGFR)-targeted drug, cetuximab. Herein, we studied the anti-cancer potency of SG compared to cetuximab. Biological studies demonstrated SG and cetuximab had similar inhibition mechanisms in CCA cells by down-regulating EGFR/ERK pathway, and the combined treatment induced a greater inhibition effect. The molecular docking study revealed that SG binds to the dimerization domain of EGFR, and this was confirmed by dimerization assay, which showed that SG inhibited ligand-induced EGFR dimer formation. Synchrotron FTIR microspectroscopy was employed to examine alterations in cellular macromolecules after drug treatment. The SR-FTIR-MS elicited similar spectral signatures of SG and cetuximab, pointing towards the bands of RNA/DNA, lipids, and amide I vibrations, which were inconsistent with the changes of signaling proteins in CCA cells after drug treatment. Thus, this study demonstrates the underlined anti-cancer mechanism of SG by interfering with EGFR dimerization. In addition, we reveal that FTIR signature spectra offer a useful tool for screening anti-cancer drugs’ effect.

【 授权许可】

Unknown