4.7 Article

Steroidal saponins from Trillium tschonoskii rhizome repress cancer stemness and proliferation of intrahepatic cholangiocarcinoma

Journal

BIOORGANIC CHEMISTRY
Volume 121, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2022.105679

Keywords

Trillium tschonoskii; Melanthiaceae; Steroidal saponin; Intrahepatic cholangiocarcinoma; Cancer stem cells; Organoids

Funding

  1. National Natural Science Foundation of China [81772617, 82173183, 82074008]
  2. National Science and Technology Major Project [2017ZX09301072]
  3. Great Wall Scholar Project [CITTCD20190311]

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A study has shown that steroidal glycosides derived from Trillium tschonoskii rhizomes have potential implications in the therapy of human intrahepatic cholangiocarcinoma (ICC) by significantly repressing tumor colony and sphere formation, as well as inhibiting cancer stem markers.
A phytochemical study was carried out on the extract of Trillium tschonoskii rhizomes, resulting in the isolation of thirty-six steroidal glycosides (1-36). Their structures were established mainly by spectroscopic analyses as well as necessary chemical evidence, of which 1-25 were identified as new analogues. Herein, all the isolated ana-logues were screened for the cytotoxicity against intrahepatic cholangiocarcinoma (ICC) cell lines of HuCCT1 and RBE through tumor colony formation and CCK-8 survival analysis, and the results demonstrated that three compounds 9, 12, and 26 significantly repressed tumor colony and sphere formation in both cell lines, respec-tively. Furthermore, the three analogues possessed a remarkable inhibitory role of organoid formation estab-lished from hydrodynamic induced mouse primary intrahepatic cholangiocarcinoma. Moreover, the functional assays of flow cytometry analysis, cancer stemness related gene expression, and western blotting assays all indicated that compound 26 could significantly repress cancer stem markers. Taken together, these results demonstrate that steroidal glycosides derived from T. tschonoskii rhizomes could be potentially implicated in human ICC therapy.

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