title: 5-Aminolevulinic acid enhances cell death under thermal stress in certain cancer cell lines.
abstract: 5-aminolevulinic acid (5-ALA) is contained in all organisms and a starting substrate for heme biosynthesis. Since administration of 5-ALA specifically leads cancer cells to accumulate protoporphyrin IX (PpIX), a potent photosensitizer, we tested if 5-ALA also serves as a thermosensitizer. 5-ALA enhanced heat-induced cell death of cancer cell lines such as HepG2, Caco-2, and Kato III, but not other cancer cell lines including U2-OS and normal cell lines including WI-38. Those 5-ALA-sensitive cancer cells, but neither U2-OS nor WI-38, accumulated intracellular PpIX and exhibited an increased reactive oxygen species (ROS) generation under thermal stress with 5-ALA treatment. In addition, blocking the PpIX-exporting transporter ABCG2 in U2-OS and WI-38 cells enhanced their cell death under thermal stress with 5-ALA. Finally, a ROS scavenger compromised the cell death enhancement by 5-ALA. These suggest that 5-ALA can sensitize certain cancer cells, but not normal cells, to thermal stress via accumulation of PpIX and increase of ROS generation.
authors.affiliation: a Department of Bioscience , Tokyo University of Agriculture , Tokyo , Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Chibazakura
authors.forename: Yui
authors.initials: Y
authors.lastname: Toriyabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujii
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Takahashi
authors.forename: Mariko
authors.initials: M
authors.lastname: Kawakami
authors.forename: Haruna
authors.initials: H
authors.lastname: Kuwamura
authors.forename: Hazuki
authors.initials: H
authors.lastname: Haga
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Ogura
authors.forename: Fuminori
authors.initials: F
authors.lastname: Abe
authors.forename: Motowo
authors.initials: M
authors.lastname: Nakajima
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005294:Ferrochelatase / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018869:Heat-Shock Response / Q000187:drug effects*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D033862:Iron-Binding Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000096923:Frataxin
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000622:Aminolevulinic Acid; D005294:Ferrochelatase; D033862:Iron-Binding Proteins; D009363:Neoplasm Proteins; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D000096923:Frataxin; C116614:ABCG2 protein, human; C028025:protoporphyrin IX
keywords: 5-aminolevulinic acid; cancer; protoporphyrin IX; thermal stress