title: ATP citrate lyase (ACLY): a promising target for cancer prevention and 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.
authors.forename: Amrita Devi
authors.initials: AD
authors.lastname: Khwairakpam
authors.forename: Mayengbam Singh
authors.initials: MS
authors.lastname: Shyamananda
authors.forename: Bethsebie Lalduhsaki
authors.initials: BL
authors.lastname: Sailo
authors.forename: Sivakumar Raju
authors.initials: SR
authors.lastname: Rathnakaram
authors.forename: Ganesan
authors.initials: G
authors.lastname: Padmavathi
authors.forename: Jibon
authors.initials: J
authors.lastname: Kotoky
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India. kunnumakkara@iitg.ernet.in.
authors.forename: Ajaikumar B
authors.initials: AB
authors.lastname: Kunnumakkara
mesh_terms: D001275:ATP Citrate (pro-S)-Lyase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D001275:ATP Citrate (pro-S)-Lyase