Sparfosic acid trisodium

Sparfosic acid trisodium, is a potent inhibitor of aspartate transcarbamoyl transferase, with anti-tumor and antimetabolite activity. Aspartate transcarbamoyl transferase catalyzes the second step of de novo pyrimidine biosynthesis[1][2].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

Research Areas >> Metabolic Disease

Sparfosic acid (PALA) treatment causes apoptosis in the resistant Br1 cells[1]. Sparfosic acid (PALA, 300 µM) shows progressive accumulation of cells in S phase and activation of an apoptotic pathway leading to cell death[1]. Cell Cycle Analysis[1] Cell Line: Br-l and L-2 cell lines established from metastasis in nude mouse injected with the human tumor cell line MDA-MB-435. Concentration: 300 µM. Incubation Time: 12, 24 and 48 h. Result: Cells were predominantly in S phase in both the cell lines, although slightly higher proportion of cells in S phase were noted in L-2 than Brl-3prl cells. Western Blot Analysis[1] Cell Line: Br-l and L-2 cell lines. Concentration: 300 µM. Incubation Time: 4, 10 and 24 h. Result: There was moderate difference in the level of phosphorylated Rb proteins seen in the two cell types. Marked increase in the amount of cyclin A protein was detected in the L-2 cells undergoing apoptosis with the highest level detected at 10 h post-drug treatment. In contrast, there was no increase in the level of cyclin A seen in the Brl-3prl cells. Cyclin E protein was found elevated in the L-2 cells and Brl-3prl cells compared to their respective controls.

[1]. Wang J, et al. Elevated cyclin A associated kinase activity promotes sensitivity of metastatic human cancer cells to DNA antimetabolite drug. Int J Oncol. 2015 Aug;47(2):782-90.

[2]. Angela D. Morris, et al. A New, Efficient, Two Step Procedure for the Preparation of the Antineoplastic Agent Sparfosic Acid