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Recent Patents on Anti-Cancer Drug Discovery

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ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

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Research Article

SSPH I, A Novel Anti-cancer Saponin, Inhibits EMT and Invasion and Migration of NSCLC by Suppressing MAPK/ERK1/2 and PI3K/AKT/ mTOR Signaling Pathways

Author(s): Jinling Zhou, Jian Luo, Rizhi Gan, Limin Zhi, Huan Zhou, Meixian Lv, Yinmei Huang and Gang Liang*

Volume 19, Issue 4, 2024

Published on: 17 January, 2024

Page: [543 - 555] Pages: 13

DOI: 10.2174/0115748928283132240103073039

Price: $65

Abstract

Background: Saponin of Schizocapsa plantaginea Hance I (SSPH I)a bioactive saponin found in Schizocapsa plantaginea, exhibits significant anti-proliferation and antimetastasis in lung cancer.

Objective: To explore the anti-metastatic effects of SSPH I on non-small cell lung cancer (NSCLC) with emphasis on epithelial-mesenchymal transition (EMT) both in vitro and in vivo.

Methods: The effects of SSPH I at the concentrations of 0, 0.875,1.75, and 3.5 μM on A549 and PC9 lung cancer cells were evaluated using colony formation assay, CCK-8 assay, transwell assay and wound-healing assay. The actin cytoskeleton reorganization of PC9 and A549 cells was detected using the FITC-phalloidin fluorescence staining assay. The proteins related to EMT (N-cadherin, E-cadherin and vimentin), p- PI3K, p- AKT, p- mTOR and p- ERK1/2 were detected by Western blotting. A mouse model of lung cancer metastasis was established by utilizing 95-D cells, and the mice were treated with SSPH I by gavage.

Results: The results suggested that SSPH I significantly inhibited the migration and invasion of NSCLC cells under a non-cytotoxic concentration. Furthermore, SSPH I at a non-toxic concentration of 0.875 μM inhibited F-actin cytoskeleton organization. Importantly, attenuation of EMT was observed in A549 cells with upregulation in the expression of epithelial cell marker E-cadherin and downregulation of the mesenchymal cell markers vimentin as well as Ncadherin. Mechanistic studies revealed that SSPH I inhibited MAPK/ERK1/2 and PI3K/AKT/mTOR signaling pathways.

Conclusion: SSPH I inhibited EMT, migration, and invasion of NSCLC cells by suppressing MAPK/ERK1/2 and PI3K/AKT/mTOR signaling pathways, suggesting that the natural compound SSPH I could be used for inhibiting metastasis of NSCLC.

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