(S)-10-Hydroxycamptothecin Inhibits EMT-evoked Osteosarcoma Cell Growth and Metastasis by Activating the HIPPO Signaling Pathway

Comb Chem High Throughput Screen. 2024;27(15):2239-2248. doi: 10.2174/0113862073263020231220043405.

Abstract

Background: Osteosarcoma is the most common primary bone cancer in children and adolescents with high metastatic ability.

Aim: This study aimed to explore the inhibitory effects of (S)-10-hydroxycamptothecin (HCPT) on osteosarcoma cell growth and metastasis as well as the underlying mechanism.

Methods: The osteosarcoma cells of 143B and U-2 OS (U-2), treated with HCPT (20, 100, or 300 nM), underwent detections, such as CCK-8, flow cytometry, Transwell, wound healing, and immunoblotting. EMT-related key proteins, like N-cadherin, Snail, and Vimentin, were found to be down-regulated, while E-cadherin was up-regulated dose-dependently in HCPT-exposed 143B and U-2 cells. Additionally, incubation of 143B and U-2 cells with HCPT for 3 hours dosedependently reduced the expression ratios of p-LATS1/LATS1, p-MST1/MST1, p-YAP/YAP, and p-TAZ/TAZ.

Results: Taken together, our study has demonstrated HCPT to inhibit osteosarcoma growth and metastasis potentially by activating the HIPPO signaling pathway and reversing EMT.

Conclusion: HCPT might be a candidate agent for the prevention and treatment of osteosarcoma.

Keywords: (S)-10-hydroxycamptothecin; EMT; HIPPO; Osteosarcoma; large tumor suppressor.; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Camptothecin* / analogs & derivatives
  • Camptothecin* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Epithelial-Mesenchymal Transition* / drug effects
  • Hippo Signaling Pathway* / drug effects
  • Humans
  • Osteosarcoma* / drug therapy
  • Osteosarcoma* / metabolism
  • Osteosarcoma* / pathology
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction* / drug effects

Substances

  • Camptothecin
  • 10-hydroxycamptothecin
  • Protein Serine-Threonine Kinases