title: Targeting tumour energy metabolism potentiates the cytotoxicity of 5-aminolevulinic acid photodynamic therapy.
abstract: BACKGROUND
  Cancerous cells usually exhibit increased aerobic glycolysis, compared with normal tissue (the Warburg effect), making this pathway an attractive therapeutic target.
  
  
  METHODS
  Cell viability, cell number, clonogenic assay, reactive oxygen (ROS), ATP, and apoptosis were assayed in MCF-7 tumour cells and corresponding primary human mammary epithelial cells (HMEC).
  
  
  RESULTS
  Combining the glycolysis inhibitors 2-deoxyglucose (2DG; 180 mM) or lonidamine (300 μM) with 10 J cm(-2) 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) increases MCF-7 cytotoxicity (by 3.5-fold to 70% death after 24 h, and by 10-fold in 9-day clonogenic assays). However, glycolysis inhibition only slightly increases HMEC PDT cytotoxicity (between two-fold and three-fold to a maximum of 9% death after 24 h). The potentiation of PDT cytotoxicity only occurred if the glycolysis inhibitors were added after ALA incubation, as they inhibited intracellular accumulation of photosensitiser if coincubated with ALA.
  
  
  CONCLUSIONS
  As 2DG and lonidamine are already used as cancer chemotherapeutic agents, our results are directly translatable to combination therapies with existing topical PDT.
authors.affiliation: Department of Life, Health & Chemical Sciences, The Open University, Walton Hall, Milton Keynes MK7 6AA, UK. j.p.golding@open.ac.uk
authors.forename: J P
authors.initials: JP
authors.lastname: Golding
authors.forename: T
authors.initials: T
authors.lastname: Wardhaugh
authors.forename: L
authors.initials: L
authors.lastname: Patrick
authors.forename: M
authors.initials: M
authors.lastname: Turner
authors.forename: J B
authors.initials: JB
authors.lastname: Phillips
authors.forename: J I
authors.initials: JI
authors.lastname: Bruce
authors.forename: S G
authors.initials: SG
authors.lastname: Kimani
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000008:administration & dosage; D000963:Antimetabolites / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D003847:Deoxyglucose / Q000008:administration & dosage; D004334:Drug Administration Schedule; D006019:Glycolysis / Q000187:drug effects*; D006593:Hexokinase / Q000037:antagonists & inhibitors; D006801:Humans; D007191:Indazoles / Q000008:administration & dosage; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000166:cytology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage; D017382:Reactive Oxygen Species / Q000378:metabolism; D014410:Tumor Stem Cell Assay
chemical_list: D000963:Antimetabolites; D000970:Antineoplastic Agents; D007191:Indazoles; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D000622:Aminolevulinic Acid; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D006593:Hexokinase; C016371:lonidamine