title: Telomelysin shows potent antitumor activity through apoptotic and non-apoptotic cell death in soft tissue sarcoma cells.
abstract: This study investigated the pathway underlying the antitumor activity of telomelysin, a telomerase-dependent, replication-selective oncolytic adenovirus, in soft tissue sarcoma cells. Treatment with telomelysin alone resulted in simultaneous induction of apoptosis and autophagy, whereas cotreatment with telomelysin and 3-methyladenine significantly reduced cell viability and increased apoptosis and the cellular ATP level compared to treatment with telomelysin alone, indicating that telomelysin-mediated autophagy is a death-protective but not death-promoting process. Cotreatment with Z-Val-Ala-Asp-CH2F significantly increased cellular ATP depletion compared to telomelysin-alone treatment while inhibiting telomelysin-induced apoptosis and having no significant effect on cell viability, indicating that it promotes transition from apoptotic to necrotic cell death.
authors.affiliation: Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Gui-Dong
authors.initials: GD
authors.lastname: Li
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawashima
authors.forename: Akira
authors.initials: A
authors.lastname: Ogose
authors.forename: Takashi
authors.initials: T
authors.lastname: Ariizumi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Hotta
authors.forename: Ryozo
authors.initials: R
authors.lastname: Kuwano
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Urata
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Naoto
authors.initials: N
authors.lastname: Endo
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000256:Adenoviridae / Q000378:metabolism*; D000257:Adenoviridae Infections / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000502:physiology*; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy* / Q000821:virology*; D019098:Telomerase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C025946:3-methyladenine; D000255:Adenosine Triphosphate; C509186:TERT protein, human; D019098:Telomerase; D000225:Adenine