Evaluating AST Cytotoxicity Compared to As(III)

Example 6

The AST cytotoxicity was evaluated and compared with that of inorganic As(III) using five different types of human cell lines from major organs/tissues: HEK293, immortalized embryonic kidney cells; THP-1, monocytes derived from an acute monocytic leukemia patient; macrophage, macrophage-like cells differentiated from THP-1; HepG2, immortalized cells isolated from a hepatocellular carcinoma; and Caco-2, immortalized cell line derived from a colorectal adenocarcinoma patient (FIG. 5). The results show that AST has much lower cytotoxicity in human cells than As(III). The LC₅₀ values of AST on all the tested cell lines except Caco2 were greater than 250 μM. Caco-2 was relatively more sensitive to AST with a lower LC₅₀ value (150-200 μM). In contrast, the LC₅₀ values of As(III) on all the tested cell lines except macrophage were lower than 25 μM, while that of macrophage was higher (100 μM), suggesting that AST is >10 times less cytotoxic than As(III). AST at 100 μM completely inhibits PfGS-I activity (FIG. 2C), P. falciparum proliferation in blood (FIG. 3) and transmission to mosquitoes (FIG. 4A), but had little effect on most of the tested human cell lines (FIG. 5). Thus, AST is effective against the malaria parasite with limited effect on human cells.