Work

Longikaurin A, a natural ent-kaurane, suppresses proliferation, invasion and tumorigenicity in oral squamous cell carcinoma cell by via inhibiting PI3K/Akt pathway in vitro and in vivo

Year: 2024

Type: article

Abstract: Background: Longikaurin A (LK-A), a naturally occurring ent-kaurane diterpenoid, has been identified as a promising anti-cancer agent.This study aims to elucidate the anti-tumorigenic effects of LK-A on oral squamous cell carcinoma (OSCC) cells and to unravel its underlying mechanisms.Methods: In vitro assays, including CCK-8 and EdU, were performed to assess cell viability and proliferation.Transwell migration and invasion assays evaluated cell mobility and invasive potential.Apoptotic effects were analyzed using Annexin V-FITC/PI staining and TUNEL assays.Western blot analysis was conducted to examine protein expression related to cell cycle, apoptosis, and the PI3K/Akt signaling pathway.In vivo experiments involved treating mouse xenograft models with LK-A and evaluating tumor growth and signaling pathway inhibition through immunohistochemistry and Western blot assays.Results: LK-A significantly suppressed cell viability and proliferation in a dose-dependent manner, with IC50 values of 4.36 μM and 4.93 μM at 24 h, and 1.98 μM and 2.89 μM at 48 h for CAL27 and TCA-8113 cells, respectively.EdU assays revealed a reduction in the EdU positive rate, and cell cycle analysis showed G2/M phase arrest.Western blot analysis confirmed decreased expression of CyclinB1 and Cdc2.LK-A significantly inhibited OSCC cell mobility and invasive potential, with downregulation of MMP-2 and MMP-9 expression.Apoptotic effects were confirmed by increased apoptosis, upregulation of Bax and cleaved caspase-3, and downregulation of Bcl-2.LK-A suppressed the PI3K/AKT signaling pathway, as evidenced by reduced phosphorylation of PI3K, AKT, and mTOR.The AKT activator SC79 reversed the antiproliferative and pro-apoptotic effects of LK-A.In vivo, LK-A significantly inhibited tumor growth in mouse xenograft models, with reduced tumor weights and volumes, and no significant loss in body weight.Immunohistochemistry and Western blot assays confirmed the inhibition of p-Akt and Ki-67 expression.Conclusion: These findings suggest that LK-A exerts potent antiproliferative, anti-migratory, and pro-apoptotic effects on OSCC cells through the suppression of the PI3K/AKT signaling pathway, demonstrating its potential as a therapeutic agent for OSCC.

Source: Journal of Cancer

DOI: 10.7150/jca.102125

Authors: Yiming Luo, Zixuan Wang, Yufei Li, Linlin Zhang

Institutions: Nanjing Medical University, Xuzhou Medical College, Jiangsu Cancer Hospital, Yancheng First People's Hospital

Language: English

Topic: Bioactive Natural Diterpenoids Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,337