Chemopreventive effects of Rheum webbianum against colorectal cancer via modulation of Wnt/beta-catenin and TGF-beta signaling: Insights from in-vitro and in-vivo studies

Background: Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, largely influenced by lifestyle and environmental factors. The search for safe, natural chemopreventive agents remains a key research priority. Rheum webbianum Royle (RW), a Himalayan medicinal plant with notable ethnopharmacological significance, has shown promising anticarcinogenic activity in prior studies. Building on our earlier findings demonstrating its protective effects against DMH-induced colon carcinogenesis, the present study further explores the anticancer potential of RW ethanolic extract, focusing on its influence on molecular pathways and rectal tissue morphology. Methods: The ethanolic extract of RW was assessed using both in-vitro and in-vivo approaches. In HT-29 colorectal adenocarcinoma cells, cytotoxicity and wound-healing assays were used to examine antiproliferative and antimigratory effects. Western blotting analyzed alterations in beta-catenin and TGF-beta1 expression. In-vivo evaluation was performed using a 1,2-dimethylhydrazine (DMH)-induced CRC rat model to investigate molecular modulation and histopathological alterations in rectal tissues. Results: In-vitro , RW extract markedly reduced HT-29 cell viability in a dose- and time-dependent manner, reaching approximately 80% inhibition at 200 µg/mL, and significantly impaired cancer cell migration. In-vivo , RW treatment downregulated beta-catenin and TGF-beta1 expression, indicating inhibition of oncogenic and pro-metastatic signaling.Histopathology: Microscopic examination revealed marked restoration of rectal tissue architecture in RW-treated groups compared to DMH-only rats. RW-treated animals showed reduced epithelial disruption, congestion, inflammatory infiltration, crypt abscesses, and dysplasia, while DMH-only groups exhibited severe mucosal damage, irregular glandular organization, and extensive inflammatory lesions with crypt abscesses and dysplasia. These findings suggest the protective efficacy of RW extracts in preventing DMH-induced colorectal tissue degeneration. Conclusion: The ethanolic extract of Rheum webbianum demonstrates strong chemopreventive potential against colorectal carcinogenesis by suppressing tumor cell proliferation, migration, and aberrant activation of Wnt/beta-catenin and TGF-beta signaling pathways, along with restoring rectal tissue integrity. These outcomes support RW as a promising natural candidate for colorectal cancer prevention and integrative therapeutic development.