Figure 8.

Proposed model for the synergistic effect of 5-FU and curcumin: 5-FU is a well-known inhibitor of TS but also leads to the upregulation of the same on prolonged exposure. It also activates NF-κB, Akt and MAPKs in several cell systems. This study postulates that TS-dependent NF-κB upregulation by 5-FU and its downregulation by curcumin have an important role in regulating the synergistic effect of 5-FU and curcumin. It also confirms that Akt and MAPK pathways do not have any regulatory role in the synergism, although they are activated by 5-FU and downregulated by curcumin. The bold lines illustrate signaling pathways regulating the synergism and dotted lines indicate pathways not involved in the synergism