Tamarixetin Suppresses Colorectal Cancer Progression by Targeting DPP7-Mediated WNT3A/β-Catenin Signalling Pathway

Area of Science:

• Oncology
• Natural Product Chemistry
• Molecular Biology

Background:

• Conventional chemotherapy offers limited benefits for colorectal cancer (CRC) patients.
• Natural compounds show promise as anti-cancer agents with fewer side effects.
• The anti-cancer potential of Tamarixetin, a flavonol from Azadirachta indica, against CRC is unexplored.

Purpose of the Study:

• To evaluate the efficacy of Tamarixetin in suppressing colorectal cancer progression.
• To elucidate the underlying molecular mechanisms of Tamarixetin's anti-cancer effects.
• To validate Tamarixetin's therapeutic potential in preclinical CRC models.

Main Methods:

• In vitro assays using CRC cell lines (HT-29, HCT-116) and normal colonic cells (NCM460).
• In vivo studies using CRC xenografts.
• Validation with patient-derived organoids.
• Analysis of DPP7 expression and WNT3A/β-catenin signaling pathway.

Main Results:

• Tamarixetin significantly inhibited CRC cell proliferation, migration, and invasion in a dose-dependent manner.
• Tamarixetin demonstrated minimal toxicity to normal colonic cells.
• Tumor growth in CRC xenografts was reduced, and CRC cells were sensitized to Oxaliplatin.
• Tamarixetin suppressed DPP7 expression, leading to downregulation of the WNT3A/β-catenin pathway.

Conclusions:

• Tamarixetin exhibits potent anti-cancer properties against colorectal cancer.
• The mechanism involves the inhibition of DPP7 and subsequent downregulation of the WNT3A/β-catenin signaling pathway.
• Tamarixetin represents a promising natural compound for novel CRC therapeutic strategies.