Abstract
Prodigiosins have been shown to have anticancer activities. 5-Fluorouracil (5-FU) is broadly used chemotherapeutic drug that treats different solid tumors including breast cancer but has low response rates and a variety of side effects. In this study, we evaluated the anticancer properties of prodigiosins in a murine model "Ehrlich tumor" and tested whether it can be added to 5-FU to potentiate its effects. Markers of oxidative stress; MDA, NO, and GSH levels were evaluated as well as antioxidant enzyme activities of CAT SOD, GR, and GPx. The levels of Bax, Bcl-2, PCNA, and NF-kappa B proteins were measured using ELISA kits. The mRNAs of p53 and Cdc2 and Casp3 were quantitatively measured by real-time PCR and ELISA respectively. Cell cycle analysis was performed using flow cytometery. Prodigiosins did not influence tumor volume. Prodigiosins have not induced oxidative stress while 5-FU did increase MDA, NO but decreased GSH levels. The combination prodigiosins and 5-FU did reduce oxidative stress markers; MDA, NO and increased GSH levels. Prodigiosins significantly increased CAT only while 5-FU did decreased SOD, CAT, GPx, and GR. The combination prodigiosins and 5-FU increased the levels of these enzymes again. Prodigiosins increased the Bax/Bcl-2 ratio while the combination deceased it. In conclusion, prodigiosins have pronounced anticancer properties but their combination with 5-FU decreased oxidative stress exerted by 5-FU but weakened the apoptotic effects of 5-FU. Prodigiosins could affect a key mechanism through which 5-FU exerts its tumor inhibitory effects.