TNF and colorectal carcinoma: Interestingly, the natural substance up-regulates p53 including its post-translational modification in consistence with its pro-oxidant action [71], and down-regulates the enzymatic activity of cyclooxygenase (COX)-2 [72] as well as the liberation of cytokines such as tumor necrosis factor (TNF)-α, TNF-β [73] or interleukin (IL)-6 [74] that are related to phenotypic and metabolic plasticity in the CRC-TME (Table 1).