Investigating the combinatory effect of Sclerocarya birrea with doxorubicin against selected colorectal cancer cell lines

Abstract

Introduction: Colorectal cancer incidences continue to increase annually, worldwide. Herbal plants with antiproliferative properties received research interest as agents that can be adjuvant therapies with chemotherapy drugs to enhance their efficacy and reverse drug resistance. Methods: Sclerocarya birrea ethanolic (SBE) and aqueous (SBW) extracts combined with doxorubicin (DOX) against drug-sensitive and drug-resistant colorectal cancer cells were investigated for their potential adjuvant and drug resistance reversal. The extracts were assessed for their potential anticancer activities on HCT15 and HT29 cell lines as well as their doxorubicin potentiating and drug resistance reversal effects respectively. The extracts were assessed for their cytotoxicity on normal 3T3-L1 fibroblast cells. Results: Both SBE and SBW extracts exhibited no toxicity against normal 3T3 cells and showed low activity on the HT29 cell line. Contrarily, resistant HCT15 cells showed moderate to low activity with significantly higher inhibitory concentration (IC)50 values. The combination of SBE with DOX and SBW with DOX resulted in antagonistic interactions, causing an increase in IC50 values for HT29 and HCT15 cells. In contrast, the combination of DOX and verapamil (VER) produced an additive effect, with no change in their IC50 values. Conclusion: Based on the findings from the combination treatment, the SBE and SBW extracts demonstrated higher efficacy and synergistic effects combined with DOX at IC75 compared to the combination of DOX and VER, suggesting their potential as anticancer agents. However, further research on both the SBE and SBW extracts’ mechanisms of action and in vivo effects is warranted.

Keywords

• Colorectal cancer
• Doxorubicin drug resistance
• Sclerocarya birrea
• Synergy
• Verapamil