Development of cancer treatment without side effects through elucidation of cancer-specific ROS control/centrosome checkpoint.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07617
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: Kato Jun-ya 奈良先端科学技術大学院大学, 先端科学技術研究科, 教授 (00273839)
• Co-Investigator(Kenkyū-buntansha): 加藤 規子 奈良先端科学技術大学院大学, 先端科学技術研究科, 特任准教授 (10252785)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がん抑制 / 細胞周期 / 副作用

Outline of Final Research Achievements

The candidate compound PGV-1 induces an increase in ROS levels and cell cycle arrest at the M phase through inhibition of the centrosome checkpoint function, leading to apoptosis in cancer cells. However, it exhibits low proliferation inhibitory effects on normal cells and is extremely low in toxicity. In this study, we analyzed the target molecules obtained from the analysis of interacting factors to elucidate the molecular nature of the cancer cell-specific centrosome checkpoint. The target candidate molecules of PGV-1 were found to be present in the centrosome, and genetic knockout halted the cell cycle at the M phase. Additionally, heterozygous cells exhibited increased sensitivity to PGV-1 in vitro and lost tumor-forming ability in nude mice in vivo. Therefore, we concluded that PGV-1 acts on the cancer cell-specific ROS-dependent centrosome checkpoint through these target candidate molecules, exerting anticancer effects.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で対象とする抗がん剤候補低分子化合物PGV-1が標的とする「がん細胞特異的ROS依存的中心体チェックポイント」は、副作用のない抗がん剤を開発するための標的としてかなり有望である。従って、実現した場合、現在の臨床現場での懸念事項（副作用による致死、適用患者の限定、治療中の社会活動からの離脱）から逃れることができる。