ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1623153
Dehydrozaluzanin C inhibits colon cancer cell proliferation, apoptosis and cycle arrest through peroxisome proliferator-activated receptor γ (PPARγ) activation
Provisionally accepted
- 1Center of Clinical Pharmacy, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
- 2School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, Yunnan, China, Kunming, Yunnan, China, China
- 3Naval Medical University, Shanghai, China
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Dehydrozaluzanin C (DC) is a sesquiterpene lactone isolated from Asteraceae plant Ainsliaea macrocephala. To investigate the antitumor effects of DC and possible molecular mechanisms for treating cancer. The antitumor effect of DC was studied using HT-29 and HCT-116 human colon tumor cell lines and Balb/c nude mice models. The anti-proliferative, proapoptotic effects, and cycle arrest of DC were observed by cell viability, colony formation, apoptosis, and cycle assays. The changes of protein expression level were examined by western blot analysis. The transcription activity of PPARγ was determined by Luciferase reporter assay. The role of PPARγ activation in the antitumor activity of DC was verified using PPARγ antagonist GW9662 and si-PPARγ HT-29 cells. DC treatment significantly decreased colon tumor cell viability, cell clone number, and increased apoptosis rate and arrested cell cycle at S phase. Furthermore, DC treatment significantly decreased Bcl-2, CDK2, and cyclin A2 protein levels while increasing the expression of cleaved caspase 3 and Bax in HT-29 and HCT-116 cells. Further investigations indicated that cell survival, induction of apoptosis, and cycle arrest by DC could be significantly reversed following treatment with the PPARγ antagonist GW9662 or in si-PPARγ cells. In vivo, DC treatment significantly decreased the weight and volume of xenograft tumor tissues in mice and apoptosis-related protein levels. The results suggest that DC effectively inhibits colon tumor cell proliferation, clone formation, apoptosis, and cell cycle arrest through PPARγ activation. These results support the potential of DC as an anti-tumor lead compound for further investigation.
Keywords: Dehydrozaluzanin C, Colon Cancer, apoptosis induction, Cycle arrest, PPARγ activation
Received: 05 May 2025; Accepted: 28 Aug 2025.
Copyright: © 2025 Li, Li, Zhu, Li, Xu, Zu, Li and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xian-Peng Zu, Naval Medical University, Shanghai, China
Xian Li, School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, Yunnan, China, Kunming, Yunnan, China, China
Yun-Heng Shen, Naval Medical University, Shanghai, China
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