Figure 3.

Pathways analysis of the proteins listed in Table 1 by means of the Ingenuity software. Mitochondrial dysfunction pathway (a) and granzyme B (GZB) signaling pathway (b) are proposed according to the structured network knowledge-based strategy. In (a), increase in the permeability of VDVC proteins in the outer mitochondrial membrane is assumed to allow for CYTC and, therefore, relevant to mitochondrial dysfunction and apoptosis. The VDVC-mediated apoptosis involves the formation of apoptosome and an activation of the caspase cascade. PRDX3 acts as an antioxidant protein to catalyze the degradation/reduction of hydrogen peroxide to water. Oxidative stress promotes the formation of ROS in mitochondrial complexes 1 to 4 and can cause mitochondrial damage. PARK7 acts as an antioxidant player and antagonizes the loss of mitochondrial function. In (b), GZB exerts its apoptotic function via the BID-dependent and BID-independent pathways. In BID-dependent route, GZB degrades BID to generate its active truncated BID (tBID), thereby inducing cell death via the formation of apoptosome and activation of caspases. In BID-independent route, GZB can activate different caspases and caspase substrates (e.g., LMNB1, etc.) independent of BID cleavage, leading to apoptosis. Red and blue indicate the proteins which are up- or downregulated by the plant compound, GHTT, in Jurkat cells. Translocation (—▹), activation (⟶), inhibition (⊣), and catalysis (—⋄) are indicated.