Complementary effects of Polygonum minus extract in combination with 5-fluorouracil in CT26 murine colon cancer cell line in vitro and in vivo

Colon cancer (CC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Treatment strategies typically begin with surgery, followed by chemotherapy, radiation therapy, or targeted therapies such as monoclonal antibodies. 5-Fluorouracil (5-FU) is a key chemotherapeutic agent in CC treatment, but its efficacy is often compromised by toxicity and drug resistance. Plant-derived compounds have gained attention for their potential to enhance chemotherapy while reducing side effects. Polygonum minus (PM), a medicinal and dietary plant, has demonstrated various bioactivities, yet its potential synergy with 5-FU remains unexplored. This study investigates the combinatorial effects of the PM hexane fraction (PM-H-H) and 5-FU on CC using both in vitro and in vivo models. In vitro assays demonstrated that PM-H-H selectively enhanced 5-FU cytotoxicity in murine CC cells (CT26), induced apoptosis, and caused cell cycle arrest at the G0/G1 phase. The combination treatment also inhibited cell migration, clonogenic survival, and spheroid growth, suggesting a potential role in suppressing metastasis. Metabolomics and proteomics analyses identified significant alterations in metabolic and signaling pathways, highlighting the mechanistic basis of the combination’s efficacy. In vivo experiments using a CT26 tumor-bearing BALB/c mouse model further confirmed these findings. The combination of PM-H-H and 5-FU significantly reduced tumor volume and weight compared to individual treatments while mitigating systemic toxicity. Histopathological analysis revealed enhanced tumor destruction and reduced adverse effects on vital organs, supporting the safety of this approach. Overall, this study provides strong evidence that PM-H-H enhances the therapeutic effects of 5-FU while reducing its toxicity. These findings suggest that PM-H-H could serve as a promising adjuvant to improve CC treatment outcomes. Further research is needed to validate its clinical potential and long-term safety.

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