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

Xiaoping Ma; Junli Chang; Xingyuan Sun; Chujie Zhou; Peng Zhao; Yanping Yang

doi:10.2174/0113862073263020231220043405

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

Comb Chem High Throughput Screen. 2024 Jan 29. doi: 10.2174/0113862073263020231220043405. Online ahead of print.

Authors

Xiaoping Ma^{1

2}, Junli Chang^{1

2}, Xingyuan Sun^{1

2}, Chujie Zhou^{1

2

2}, Peng Zhao^{1

2}, Yanping Yang^{1

2}

Affiliations

¹ Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
² Key Laboratory of theory and therapy of muscles and bones, Ministry of Education, Shanghai, 200032, China.

PMID: 38369725
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.

Method: 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.

Result: 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; Lung metastatic; Medicin; Osteosarcoma.