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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-05715-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849238759235649536 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Hyun-Ha Hwang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-42fe4fbb8b6a4eaeb35538ea14c197cc |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-42fe4fbb8b6a4eaeb35538ea14c197cc2025-08-20T04:01:25ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-05715-5Sd-021, derivatives of decursin, inhibits tumorigenesis in NSCLC by inhibiting the EGFR/STAT3 signaling pathwayHyun-Ha Hwang0Jeong-Hui Je1Hyeong-Chan Lee2Ji-Sung Yoo3Taehyoun Kim4Jung Hwan Choi5Jin Won Hong6Hae-In Lim7Ga Yoon Kim8Yun-Beom Sim9Kwang-Jin Cho10Eun-wook Choi11Chunhoo Cheon12Jae Yeol Lee13Seong-Gyu Ko14Department of Science in Korean Medicine, Graduate School, Kyung Hee UniversityDepartment of Science in Korean Medicine, Graduate School, Kyung Hee UniversityDepartment of Science in Korean Medicine, Graduate School, Kyung Hee UniversityDepartment of Science in Korean Medicine, Graduate School, Kyung Hee UniversityDepartment of Science in Korean Medicine, Graduate School, Kyung Hee UniversityResearch Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee UniversityResearch Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee UniversityDepartment of Science in Korean Medicine, Graduate School, Kyung Hee UniversityDepartment of Science in Korean Medicine, Graduate School, Kyung Hee UniversityInstitute for Research Center in Jaein R&PDepartment of Science in Korean Medicine, Graduate School, Kyung Hee UniversityInstitute for Research Center in Jaein R&PDepartment of Science in Korean Medicine, Graduate School, Kyung Hee UniversityResearch Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee UniversityDepartment of Science in Korean Medicine, Graduate School, Kyung Hee UniversityAbstract 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.https://doi.org/10.1038/s41598-025-05715-5Sd-021Decursin derivativesNon-small cell lung cancer (NSCLC)EGFR/STAT3 signaling pathway |
| spellingShingle | 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 Sd-021, derivatives of decursin, inhibits tumorigenesis in NSCLC by inhibiting the EGFR/STAT3 signaling pathway Scientific Reports Sd-021 Decursin derivatives Non-small cell lung cancer (NSCLC) EGFR/STAT3 signaling pathway |
| title | Sd-021, derivatives of decursin, inhibits tumorigenesis in NSCLC by inhibiting the EGFR/STAT3 signaling pathway |
| title_full | Sd-021, derivatives of decursin, inhibits tumorigenesis in NSCLC by inhibiting the EGFR/STAT3 signaling pathway |
| title_fullStr | Sd-021, derivatives of decursin, inhibits tumorigenesis in NSCLC by inhibiting the EGFR/STAT3 signaling pathway |
| title_full_unstemmed | Sd-021, derivatives of decursin, inhibits tumorigenesis in NSCLC by inhibiting the EGFR/STAT3 signaling pathway |
| title_short | Sd-021, derivatives of decursin, inhibits tumorigenesis in NSCLC by inhibiting the EGFR/STAT3 signaling pathway |
| title_sort | sd 021 derivatives of decursin inhibits tumorigenesis in nsclc by inhibiting the egfr stat3 signaling pathway |
| topic | Sd-021 Decursin derivatives Non-small cell lung cancer (NSCLC) EGFR/STAT3 signaling pathway |
| url | https://doi.org/10.1038/s41598-025-05715-5 |
| work_keys_str_mv | AT hyunhahwang sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT jeonghuije sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT hyeongchanlee sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT jisungyoo sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT taehyounkim sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT junghwanchoi sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT jinwonhong sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT haeinlim sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT gayoonkim sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT yunbeomsim sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT kwangjincho sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT eunwookchoi sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT chunhoocheon sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT jaeyeollee sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway AT seonggyuko sd021derivativesofdecursininhibitstumorigenesisinnsclcbyinhibitingtheegfrstat3signalingpathway |