ATP Citrate Lyase (ACLY): A Promising Target for Cancer Prevention and Treatment

Title:ATP Citrate Lyase (ACLY): A Promising Target for Cancer Prevention and Treatment

Volume: 16 Issue: 2

Author(s): Amrita Devi Khwairakpam, Mayengbam Singh Shyamananda, Bethsebie Lalduhsaki Sailo, Sivakumar Raju Rathnakaram, Ganesan Padmavathi, Jibon Kotoky and Ajaikumar B. Kunnumakkara

Affiliation:

Keywords: Acetyl-CoA, ATP citrate lyase, cancer, chemoprevention, treatment.

Abstract: ATP citrate lyase (ACLY), an important enzyme involved in lipid biogenesis linked with glucose metabolism, catalyzes the conversion of citrate to oxaloacetic acid (OAA) and acetyl-CoA. The obtained acetyl-CoA is required for lipid synthesis during membrane biogenesis, as well as for histone acetylation reactions to regulate the expression of certain proteins in aberrantly proliferating cancer cells. Studies have shown a role for ACLY in tumorigenesis whereby increased levels of the enzyme leads to increased metabolic activity via activation of Akt signaling. Increasing lines of evidence suggest that enzymes involved in lipid biogenesis play a significant role in cancer cell proliferation and progression. In many cancer types such as glioblastoma, colorectal cancer, breast cancer, non-small cell lung cancer, hepatocellular carcinoma etc., the level of ACLY has been found to be quite high as compared to normal cells. Cancer cell growth related to overexpression of ACLY can be inhibited by using chemical inhibitors or by the knockdown of ACLY gene. Inhibition of ACLY leads to changes in cancer cell metabolism that promotes tumor growth and proliferation. This review summarizes the role of ACLY in cancer development and its inhibitors in cancer treatment.

Cite this article as:

Khwairakpam Devi Amrita, Shyamananda Singh Mayengbam, Sailo Lalduhsaki Bethsebie, Rathnakaram Raju Sivakumar, Padmavathi Ganesan, Kotoky Jibon and Kunnumakkara B. Ajaikumar, ATP Citrate Lyase (ACLY): A Promising Target for Cancer Prevention and Treatment, Current Drug Targets 2015; 16 (2) . https://dx.doi.org/10.2174/1389450115666141224125117