What question did this study set out to answer?

To investigate the antitumor effects of eudesmanolides from Sphagneticola trilobata on colorectal cancer through β-catenin signalling inhibition.

May 7, 2026

Anticancer Potential of Eudesmanolides Derived from Sphagneticola trilobata against Colorectal Cancer, by Targeting β-catenin Signalling

Key Points

To investigate the antitumor effects of eudesmanolides from Sphagneticola trilobata on colorectal cancer through β-catenin signalling inhibition.
Isolation and characterization of eudesmanolides using chromatographic and spectrometric techniques.
Assessment of cell viability via various assays, including flow cytometry and immunoblot analysis.
Induction and analysis of apoptosis pathways in colorectal cancer cells, particularly HCT116.
Molecular docking studies to elucidate the interaction mechanisms of eudesmanolides with target proteins.
Toxicological evaluation in Swiss albino mice.
Eudesmanolides effectively induced apoptosis in different colorectal cancer cell lines.
The study identified extrinsic and intrinsic mechanisms of apoptosis activation by eudesmanolides.
Molecular investigations revealed inhibition of β-catenin signalling in HCT116 cells.
The antitumor potential of eudesmanolides was established through various bioassays.
Eudesmanolides demonstrated pharmacological safety in animal models.

Abstract

INTRODUCTION: The role of β-catenin signalling in the pathogenesis of Colorectal Cancer (CRC) is indisputable. In this study, we report the identification of a cytotoxic fraction that targets the β-catenin signalling axis in colorectal cancer cells. METHODS: Chromatographic and spectrometric techniques were used for the isolation and phytochemical characterization of Eudesmanolides (EDS). Cell-viability assays, flow cytometry, fluorescent microscopy, immunoblot analysis, qRT-PCR, and in silico molecular docking studies were used to analyse the antitumor potential of EDS against CRC cells. Toxicological evaluation of EDS was conducted in Swiss albino mice. RESULTS: We have isolated and characterized the bioactive fraction designated EDS, consisting of the eudesmanolides, namely wedelolide D and prostrolide A, from the Ethyl Acetate (EA) leaf extract of the plant Sphagneticola trilobata (S. trilobata). EDS was found to be highly efficacious against CRC cells and induced an apoptotic mode of cell death in different CRC cell lines. Delineation of the apoptotic pathway induced by EDS revealed extrinsic pathway activation and amplification of the apoptotic signals via the intrinsic pathway through truncated-BID. Molecular investigations revealed EDS-mediated inhibition of β-catenin signalling and PPAR-γ (peroxisome proliferator-activated receptor gamma) activation in HCT116 CRC cells. DISCUSSION: Our study revealed that EDS induced strong apoptotic signals in CRC cells, initiated at the cell surface, resulting in apoptosis involving extrinsic and intrinsic mechanisms irrespective of the p53 status or molecular phenotype of CRC cells. In addition, PPAR-γ activation by EDS resulted in the suppression of β- catenin nuclear accumulation and the subsequent inhibition of proliferative and survival signalling. Moreover, EDS was found to be pharmacologically safe. CONCLUSION: To summarize, we demonstrate, with mechanism-based evidence, the chemotherapeutic efficacy of EDS, comprising the eudesmanolides, wedelolide D, and prostrolide A, derived from S. trilobata, against CRC. The potential of these lead-structures are worth exploring for their beneficial effects in combination with other therapeutic interventions.

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Cite This Study

Johny et al. (Wed,) studied this question.

synapsesocial.com/papers/69fbe3aa164b5133a91a2eec https://doi.org/https://doi.org/10.2174/0118715206431960260123110937

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