Combined Efficacy of Cinnamomum Zeylanicum And Doxorubicin Against Leukemia Through Regulation of TRAIL And NF-Kappa B Pathways In Rat Model

Abstract Background: Recent discoveries in cancer therapeutics have proven combination therapies more effective than individual drugs. This study describes the efficacy of Cinnamomum zeylanicum and doxorubicin combination against benzene-induced leukemia. Methods and Results: Brine shrimp assay was used to assess the cytotoxicity of Cinnamomum zeylanicum, doxorubicin and their combination. After AML induction in Sprague Dawley rats, the same drugs were given to rat groups. Changes in organ weights, haematological profile, and hepatic enzymes were determined. Real-time PCR was used to elucidate the effect on the expression of STMN1, GAPDH, P53 and various TRAIL and NF-kappa B components. Cinnamomum zeylanicum reduced the cytotoxicity of doxorubicin. The combination treatment showed better anti-leukemic potential than any of the individual drugs as evident from STMN1 expression (p<0.001). It was particularly useful in reducing total white blood cell counts and recovering lymphocytes, monocytes and eosinophils along with hepatic enzymes ALT and AST (p<0.001). All doses recovered relative organ weights and improved blood parameters. The combination therapy was particularly effective in the inhibition of proliferation marker GAPDH (p<0.001) and NF-kappa B pathway components Rel-A (p<0.001) and Rel-B (p<0.05). Expressions of TRAIL components c-FLIP (p<0.001), TRAIL ligand (p<0.001) and caspase 8 (p<0.05) were also altered. Conclusion: Cinnamomum zeylanicum in combination with doxorubicin helps to counter benzene-induced cellular and hepatic toxicity and improve haematological profile. The anti-leukemic effects are potentially mediated through inhibition of GAPDH and NF-kappa B pathway and regulation of TRAIL pathway. Our data suggest the use of Cinnamomum zeylanicum with doxorubicin to improve anti-leukemic therapeutic regimes.