A comparative study of some NSAIDs with natural products: integrating in vitro anticancer efficacy, in vivo antiulcerative effect, histochemistry, and in silico analysis

Assessing the biological activities of some potential drugs and comparing their suitability for in vitro and in vivo combination therapy or in silico drug repositioning against important targets is essential for minimizing labor, costs, and time in drug development. Herein, dose- and time-dependent in vitro anticancer activity studies of anti-inflammatory drugs, including celecoxib (C), indomethacin (I), and meloxicam (M), in combination with natural products (taxifolin (T), quercetin (Q), and rutin (R)) and doxorubicin (Dox), were carried out in MDA-MB-231, BT-20, MCF-7, and HT-29 human cancer cell lines. Drug C demonstrated significant anticancer activity in cancer cells with natural products (< 40 µM) and Dox (< 5 µM). The antiulcerative effect of the most promising drug C in combination with T and R in rats was carried out. The histopathological analysis suggests that the substitution of R with T, when combined with drug C, leads to a statistically significant improvement in the amelioration of gastric mucosal injury. Additionally, in silico studies have been conducted against the important cancer drug target sphingosine kinase 1 (SphK1). The obtained results highlight that drug C and T may be potential inhibitor candidates as SphK1 inhibitors for targeted cancer therapy. Overall, the combination of drug C with T has shown promising results, anticancer effects in breast and colon cancer cells and antiulcerative effects in rats.