Strategies aiming to increase cytosolic citrate should be developed and tested in humans, knowing that experimental studies have shown that administration of citrate and/or inhibition of ACLY arrest tumor growth, inhibit the expression of the key anti-apoptotic factor Mcl-1, reverse cell dedifferentiation and increase sensibility to cisplatin.
ATP citrate lyase (ACLY), a key enzyme initiating de novo lipid synthesis, has been found to be upregulated in cancer cells, and its inhibition causes suppressive effects in a variety of tumors.
Furthermore, ACLY inhibitor SB-204990 greatly abolishes the promoting effect of CUL3 down-regulation on lipid synthesis, cell proliferation, and tumor growth.
Immunohistochemical analysis showed that phosphorylated ACL was increased in ovarian cancer tissues and that its expression correlated well with tumor grade, FIGO stage and poorer prognosis.