• Open Access

Telomelysin shows potent antitumor activity through apoptotic and non-apoptotic cell death in soft tissue sarcoma cells

Authors

  • Gui-Dong Li,

    1. Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
    2. Department of Orthopedic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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  • Hiroyuki Kawashima,

    Corresponding author
    • Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • Akira Ogose,

    1. Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • Takashi Ariizumi,

    1. Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • Tetsuo Hotta,

    1. Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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  • Ryozo Kuwano,

    1. Department of Molecular Genetics and Bioinformatics, Center for Bioresource-based Researches, Brain Research Institute, Niigata University, Niigata, Japan
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  • Yasuo Urata,

    1. Oncolys BioPharma, Inc., Tokyo, Japan
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  • Toshiyoshi Fujiwara,

    1. Division of Surgical Oncology, Department of Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
    2. Center for Gene and Cell Therapy, Okayama University Hospital, Okayama, Japan
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  • Naoto Endo

    1. Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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To whom correspondence should be addressed.

E-mail: inskawa@med.niigata-u.ac.jp

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.

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