**6. Inhibition of ASS1 activity**

The mechanisms which exhibited the loss of ASS1 activity are specifically depend on the type of cancerous cell and availability of arginine. ASS1 is a rate-limiting enzyme involved in arginine biosynthesis and has been investigated in numerous cancerous conditions such as melanoma [48], hepatocellular carcinoma [49] and pancreatic cancers [50], and the. ASS1-negative cancer cells are auxotrophic for arginine and exhibit sensitivity to arginine deprivation [51]. Cancerous cells have lack expression of ASS1 enzyme required for arginine biosynthesis which is an exogenous source for proteins synthesis and cellular growth [52]. Less ASS1 expression was recorded as a biomarker in cancer cell and for overall cellular functioning. The ASS1-deficient cancers with arginine auxotrophy have been initiated as the development of therapeutics by depriving arginine through degradation and trigger the apoptosis in arginine auxotrophic cancerous cells [53] as shown in **Figure 5**. The low levels of acetylated polyamine metabolites were found in arginosuccinate

#### **Figure 5.**

*Impact of gene ASS1 expression for cancer progression and proliferation and its down-regulation by ADI enzyme.*

synthetase-deficient cells, pinpointing the reduction in catabolism and increase the expression of polyamine biosynthetic enzymes. This metabolic reprogramming elucidates a synthetic lethal interaction between arginosuccinate synthetase loss and polyamine metabolism, which could potentially be exploited for the treatment of arginosuccinate synthetase-negative cancers [54]. The reason for down-regulation of arginosuccinate synthetase in cancer cells is not cleared properly but always remains the center of interest among the cancer researchers [55].
