Related Experiment Video
Updated: Jul 13, 2025
Preclinical Assessment of the Bioactivity of the Anticancer Coumarin OT48 by Spheroids, Colony Formation Assays, and Zebrafish Xenografts
Published on: June 26, 2018
3β-Hydroxy-12-oleanen-27-oic Acid Exerts an Antiproliferative Effect on Human Colon Carcinoma HCT116 Cells via
Jue Tu1,2, Xiang Meng1, Juanjuan Wang1
1College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Abstract:
3β-hydroxy-12-oleanen-27-oic acid (ATA), a cytotoxic oleanane triterpenoid with C14-COOH isolated from the rhizome of Astilbe chinensis, has been previously proven to possess antitumor activity and may be a promising antitumor agent. However, its molecular mechanisms of antitumor action were still unclear. This study explored the underlying mechanisms of cytotoxicity and potential target of ATA against human colorectal cancer HCT116 cells via integrative analysis of transcriptomics and network pharmacology in combination with in vitro and in vivo experimental validations. ATA significantly inhibited the proliferation of HCT116 cells in a concentration- and time-dependent manner and induced the cell cycle arrest at the G0/G1 phase, apoptosis, autophagy, and ferroptosis. Transcriptomic analysis manifested that ATA regulated mRNA expression of the genes related to cell proliferation, cell cycle, and cell death in HCT116 cells. The integrated analysis of transcriptomics, network pharmacology, and molecular docking revealed that ATA exerted cytotoxic activity via interactions with FDFT1, PPARA, and PPARG. Furthermore, FDFT1 was verified to be an upstream key target mediating the antiproliferative effect of ATA against HCT116 cells. Of note, ATA remarkably suppressed the growth of HCT116 xenografts in nude mice and displayed an apparent attenuation of FDFT1 in tumor tissues accompanied by the alteration of the biomarkers of autophagy, cell cycle, apoptosis, and ferroptosis. These results demonstrate that ATA exerted in vitro and in vivo antiproliferative effects against HCT116 cells through inducing cell apoptosis, autophagy, and ferroptosis via targeting FDFT1.
Insights
3β-hydroxy-12-oleanen-27-oic acid (ATA) shows antitumor potential against colorectal cancer. ATA inhibits cancer cell growth by inducing apoptosis, autophagy, and ferroptosis, primarily by targeting FDFT1.
Area of Science:
- Pharmacology
- Molecular Biology
- Cancer Research
Background:
- 3β-hydroxy-12-oleanen-27-oic acid (ATA), a triterpenoid from *Astilbe chinensis*, exhibits antitumor properties.
- The precise molecular mechanisms underlying ATA's cytotoxic effects remain largely unexplored.
Purpose of the Study:
- To elucidate the molecular mechanisms and identify potential targets of ATA against human colorectal cancer (CRC) HCT116 cells.
- To validate findings through integrated transcriptomics, network pharmacology, and experimental approaches.
Main Methods:
- Integrative analysis of transcriptomics and network pharmacology.
- In vitro assays for cell proliferation, cell cycle, apoptosis, autophagy, and ferroptosis.
- Molecular docking and in vivo xenograft studies in nude mice.
Main Results:
- ATA significantly inhibited HCT116 cell proliferation, inducing G0/G1 cell cycle arrest, apoptosis, autophagy, and ferroptosis.
- Transcriptomic analysis revealed ATA's regulation of genes involved in cell proliferation and death.
- FDFT1 was identified as a key upstream target mediating ATA's antiproliferative effects, confirmed by molecular docking and in vivo studies.
Conclusions:
- ATA demonstrates potent in vitro and in vivo antiproliferative activity against colorectal cancer HCT116 cells.
- ATA induces apoptosis, autophagy, and ferroptosis via targeting FDFT1, highlighting its potential as an anticancer therapeutic agent.
