Panaxadiol derivatives inhibit lung metastasis of breast cancer via DLL4-Notch signaling pathway and palmitoyl carnitine aggregation
5 affiliations
- 1Institute of Taihang Materia Medica, Shanxi University of Chinese Medicine, Jinzhong, 030600, China
- 2Jilin Medical University, Jilin, 132013, China
- 3Institute of Taihang Materia Medica, Shanxi University of Chinese Medicine, Jinzhong, 030600, China; Modern Research Center for Traditional Chinese Medicine of Shanxi University, NO.92, Wucheng Road, Taiyuan, 030006, China; Corresponding author. Institute of Taihang Materia Medica, Shanxi University of Chinese Medicine, Jinzhong, 030600, China.
- 4Institute of Taihang Materia Medica, Shanxi University of Chinese Medicine, Jinzhong, 030600, China; Corresponding author.
- 5Yanbian University, Yanji, 13300, China; Corresponding author.
Abstract
Background: As a classic traditional Chinese medicine, ginseng is widely used in cancer treatment. We found that the panaxadiol derivative 6a inhibits breast cancer cell proliferation, but its anti-metastatic effect and mechanism remain unclear. Materials and methods: Multiple breast cancer cell lines were used to assess the in vitro antiproliferative and antimigratory activities of 6a. A lung metastasis model, small animal imaging, and pathological examination were employed for in vivo efficacy evaluation. Metabolomic analysis and experimental validation focused on key metabolites and signaling pathways. Results: Compound 6a effectively inhibited proliferation and migration of breast cancer cells, showing stronger activity than panaxadiol and ginsenoside Rg3. Further metabolomic analysis revealed that the inhibitory effect of 6a on breast cancer cells was achieved by effectively regulating the “fatty acid degradation” pathway. Focusing on palmitoylcarnitine (PC), a key differential metabolite, we further analyzed its association with the DLL4-Notch signaling pathway. The results indicated that compound 6a interfered with cancer cell metastasis through the DLL4-Notch pathway and related metastasis signaling pathways, and further promoted the accumulation of PC. In in vitro validation, as the concentration of PC increased, it exhibited the same inhibitory effect on cancer cells as that of 6a. Conclusion: In conclusion, this study systematically evaluated the inhibitory effect of the ginsenoside derivative 6a on breast cancer lung metastasis. This study not only provides insights for exploring the activity of panaxadiol, but also offers evidence for the application of ginsenosides in cancer therapeutic drugs.
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BibTeX
@article{xiao2026panaxadiol,
title = {{Panaxadiol derivatives inhibit lung metastasis of breast cancer via DLL4-Notch signaling pathway and palmitoyl carnitine aggregation}},
author = {Shengnan Xiao and Lei Xu and Lianmei Liu and Tianyi Zhang and Xueqian Bai and Zhenyu Li and Zhi Chai and Yuqing Zhao},
journal = {Journal of Ginseng Research},
year = {2026},
month = aug,
doi = {10.1016/j.jgr.2026.101122},
url = {https://doi.org/10.1016/j.jgr.2026.101122},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Panaxadiol derivatives inhibit lung metastasis of breast cancer via DLL4-Notch signaling pathway and palmitoyl carnitine aggregation
AU - Shengnan Xiao
AU - Lei Xu
AU - Lianmei Liu
AU - Tianyi Zhang
AU - Xueqian Bai
AU - Zhenyu Li
AU - Zhi Chai
AU - Yuqing Zhao
PY - 2026
DA - 2026/08/03
JO - Journal of Ginseng Research
DO - 10.1016/j.jgr.2026.101122
UR - https://doi.org/10.1016/j.jgr.2026.101122
AB - Background: As a classic traditional Chinese medicine, ginseng is widely used in cancer treatment. We found that the panaxadiol derivative 6a inhibits breast cancer cell proliferation, but its anti-metastatic effect and mechanism remain unclear. Materials and methods: Multiple breast cancer cell lines were used to assess the in vitro antiproliferative and antimigratory activities of 6a. A lung metastasis model, small animal imaging, and pathological examination were employed for in vivo efficacy evaluation. Metabolomic analysis and experimental validation focused on key metabolites and signaling pathways. Results: Compound 6a effectively inhibited proliferation and migration of breast cancer cells, showing stronger activity than panaxadiol and ginsenoside Rg3. Further metabolomic analysis revealed that the inhibitory effect of 6a on breast cancer cells was achieved by effectively regulating the “fatty acid degradation” pathway. Focusing on palmitoylcarnitine (PC), a key differential metabolite, we further analyzed its association with the DLL4-Notch signaling pathway. The results indicated that compound 6a interfered with cancer cell metastasis through the DLL4-Notch pathway and related metastasis signaling pathways, and further promoted the accumulation of PC. In in vitro validation, as the concentration of PC increased, it exhibited the same inhibitory effect on cancer cells as that of 6a. Conclusion: In conclusion, this study systematically evaluated the inhibitory effect of the ginsenoside derivative 6a on breast cancer lung metastasis. This study not only provides insights for exploring the activity of panaxadiol, but also offers evidence for the application of ginsenosides in cancer therapeutic drugs.
SN - 1226-8453
SN - 2093-4947
ER -