Sd-021, derivatives of decursin, inhibits tumorigenesis in NSCLC by inhibiting the EGFR/STAT3 signaling pathway

Sd-021, derivatives of decursin, inhibits tumorigenesis in NSCLC by inhibiting the EGFR/STAT3 signaling pathway

Abstract Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a significant challenge in oncology despite advances in targeted and immune-based therapies. NSCLC accounts for approximately 85% of all lung cancer cases, with five-year survival rates ranging from 4 to 17%, depending on...

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Main Authors: Hyun-Ha Hwang, Jeong-Hui Je, Hyeong-Chan Lee, Ji-Sung Yoo, Taehyoun Kim, Jung Hwan Choi, Jin Won Hong, Hae-In Lim, Ga Yoon Kim, Yun-Beom Sim, Kwang-Jin Cho, Eun-wook Choi, Chunhoo Cheon, Jae Yeol Lee, Seong-Gyu Ko
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Subjects:
Sd-021
Decursin derivatives
Non-small cell lung cancer (NSCLC)
EGFR/STAT3 signaling pathway
Online Access:https://doi.org/10.1038/s41598-025-05715-5
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Summary:Abstract Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a significant challenge in oncology despite advances in targeted and immune-based therapies. NSCLC accounts for approximately 85% of all lung cancer cases, with five-year survival rates ranging from 4 to 17%, depending on disease stage and regional factors. Chemotherapy resistance remains a major hurdle, contributing to poor patient prognosis. This study explores the therapeutic potential of Sd-021, a novel decursinol derivative, compared to its parent compound, decursin, within various NSCLC cell lines. Our results reveal that Sd-021 demonstrates enhanced anticancer activity, highlighted by a more significant reduction in cell viability, increased induction of apoptosis, and more pronounced cell cycle arrest. Notably, Sd-021 shows increased inhibition of the EGFR/STAT3 signaling pathway in EGFR wild-type cell lines, including A549, H460, and H1299 cells. Moreover, in vivo experiments employing a subcutaneous xenograft mouse model reveal that Sd-021 reduces tumor volume with minimal systemic toxicity, as indicated by histopathological assessments revealing reduced tumor proliferation and heightened apoptosis. The minimal toxicity of Sd-021 offers reassurance regarding its safety for potential clinical applications. In conclusion, these findings highlight the promise of Sd-021 as a therapeutic agent against NSCLC.
ISSN:2045-2322

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