The combination of sitagliptin and bee honey extract potentiates the anti-proliferative properties of 5-fluorouracil on Caco-2 cell line without detectable inflammatory events

Abstract

Colon cancer originates in the colon, specifically the large intestine. It carries a poor prognosis and high mortality rate due to late diagnosis and migration. Here our objective was to evaluate the anticancer effects of sitagliptin (Sita) in colon cancer using Caco-2 cells. Additionally, we examined the role of bee honey extract in modulating cancer cell division and necrotic events commonly observed during drug treatments. We monitored cell viability rate to evaluate the effect of bee honey extract compared to 5-fluorouracil (5-Fu), Sita, and their combinations. To gain further foresights into the implicated molecular interaction, we assessed the expression outline of Raf-1 and MEK, as proliferation effectors. Additionally, we examined the expression outline of p53 and Caspase 3, which are associated with programmed cell death (PCD), through western blot analysis. We identified the Raf-1 expression pattern as a likely target for the drug combination and bee honey extract (HE), which effectively controlled colon cancer cell proliferation. Our study demonstrates that honey extract, either alone or in combination with drugs, can induce PCD by restoring the p53 and CASP-3 proteins. This was accompanied by a synergistic effect on the production of apoptotic cytokines, particularly interlukine-6 (IL-6) and IL-8, in cancer cells. Moreover, the treatment modulated the levels of pro-inflammatory cytokines, including IL-1 alpha and beta and anti-inflammatory cytokines, including IL-4 and IL-10. Our findings shed light on honey extract and its combinations with 5-Fu and Sita in stimulating PCD and modulating cytokine production in Caco-2 cells.