Development of a new remedy of osteosarcoma by Salinomycin/PASS

• Project/Area Number: 17K10988
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Nihon University
• Principal Investigator: YOSHIDA Yukihiro 日本大学, 医学部, 講師 (20201022)
• Co-Investigator(Kenkyū-buntansha): 安藤 隆 山梨大学, 大学院総合研究部, 講師 (10377492) ; 鈴木 良弘 一般社団法人プラズマ化学生物学研究所, 研究部, 代表理事 (80206549)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: プラズマ / 骨肉腫 / PASS / サリノマイシン / オートファジー / ミトファジー / 骨・軟部腫瘍学 / プラズマ活性化塩溶液（PASS） / salinomycin

Outline of Final Research Achievements

Results of our study
The present study examined the molecular cell death mechanism of osteosarcoma, induced with non-thermal atmospheric pressure plasma-activated saline solution (PASS) and salinomycin (Sal), and confirmed their antitumor effects, thereby establishing a foundation for a novel osteosarcoma treatment using PASS and Sal. In conclusion, PASS and Sal were demonstrated to have potent antitumor effects on osteosarcoma by suppressing cytoprotective autophagy and inducing non-apoptotic cell death. Our results may lead to the development of an effective and safe treatment for apoptosis-resistant osteosarcoma by the combined administration of PASS and Sal.

Academic Significance and Societal Importance of the Research Achievements

転移や再発を来した骨肉腫には有効な化学療法がないのが現状である。われわれは、低温大気圧プラズマ(Cold atmospheric plasma, CAP)に注目し、低温大気圧プラズマ輸液剤（PASS：Plasma-activated salt solution）およびサリノマイシン（Sal）によって誘発される細胞死のメカニズムを分子レベルで明らかにし、PASSおよびSalは、細胞保護的なオートファジーを抑制して非アポト－シス型細胞死を誘発することにより、骨肉腫に対して高い抗腫瘍効果を示すことが明らかとなった。本研究成果は骨肉腫に対する有効かつ安全な治療法の開発として期待される。

Research Products

• [Journal Article] Cold PSM, but not TRAIL, triggers autophagic cell death: A therapeutic advantage of PSM over TRAIL (2018)
  • Author(s): Tomohisa Ito,1 Takashi Ando,2 Miki Suzuki-Karasaki,1,3 Tomohiko Tokunaga,4 Yukihiro Yoshida,1 Toyoko Ochiai,5 Yasuaki Tokuhashi,1 and Yoshihiro Suzuki-Karasaki3,6
  • Journal Title: Int J Oncol Volume: 53 Pages: 503-514
  • DOI: 10.3892/ijo.2018.4413
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mitochondrial Ca2+ removal amplifies TRAIL cytotoxicity toward apoptosis-resistant tumor cells via promotion of multiple cell death modalities (2017)
  • Author(s): 3.Takata N, Ohshima Y, Suzuki-Karasaki M, Yoshida Y, Tokuhashi Y, Suzuki-Karasaki Y
  • Journal Title: Int J Oncol Volume: 51(1) Issue: 1 Pages: 193-203
  • DOI: 10.3892/ijo.2017.4020
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Disrupting mitochondrial Ca2+ homeostasis causes tumor-selective TRAIL sensitization through mitochondrial network abnormalities (2017)
  • Author(s): 2.Ohshima Y, Takata N, Suzuki-Karasaki M, Yoshida Y, Tokuhashi Y, Suzuki-Karasaki Y.
  • Journal Title: Int J Oncol Volume: 51(4) Issue: 4 Pages: 1146-1158
  • DOI: 10.3892/ijo.2017.4096
  • Peer Reviewed / Open Access / Int'l Joint Research