Development of inhibitory method against cancer cell growth with few side effects using nutritional ingredients

• Project/Area Number: 20K05930
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 38050:Food sciences-related
• Research Institution: Aomori University
• Principal Investigator: FUKUI Masayuki 青森大学, 薬学部, 教授 (60392502)
• Co-Investigator(Kenkyū-buntansha): 金光 兵衛 国際医療福祉大学, 薬学部, 教授 (00265084)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: アポトーシス / 不飽和脂肪酸 / がん細胞 / TRAIL受容体 / Bel-2ファミリータンパク質 / 抗腫瘍作用

Outline of Research at the Start

TRAILという分子は正常細胞に影響せず、癌細胞特異的に細胞死を誘導することができる。しかし、癌細胞のなかにはTRAILが誘導する細胞死に対して感受性が低いものも存在する。そこで本研究では、ヒトが日常摂取するビタミンCや不飽和脂肪酸の摂取とTRAIL投与を併用することにより、TRAIL単独では細胞死を誘導できない癌細胞に対して、TRAILが誘導する癌細胞特異的な細胞死誘導効果を上昇させる事を証明する。さらにそのTRAIL高感受性誘導機構を解析し、副作用の少ない治療法の開発を目指す。

Outline of Final Research Achievements

A molecule called TRAIL can specifically induce cell death in cancer cells without affecting normal cells. However, some cancer cells are less sensitive to TRAIL-induced cell death. In this study, we tried to clarify that the unsaturated fatty acids that humans ingest on a daily basis increase the cancer-cell-specific cell death induced by TRAIL against cancer cells in which TRAIL alone cannot induce cell death. As a result, we found that the treatment of breast cancer cells with unsaturated fatty acids changed the expression level of Bcl-2 family proteins, which are molecules that regulate cell death.

Academic Significance and Societal Importance of the Research Achievements

不飽和脂肪酸によってTRAIL感受性を誘導できる細胞株と誘導できない細胞株の応答の違いを明らかにすることで、がん細胞の薬剤耐性獲得メカニズムを明らかにすることができ、新しい抗腫瘍薬の標的候補の探索に繋がる。また、これまでの抗腫瘍薬は正常細胞にも影響し副作用を示すものが多く、患者のQOL低下が問題となる。不飽和脂肪酸の様な栄養成分でがん細胞の細胞死感受性を上昇させ、抗腫瘍薬の投与量を下げることができる。抗腫瘍薬の副作用の影響を低減することは、患者のQOLの向上が期待できる。

Research Products

• [Journal Article] GRIM-19 is a target of mycobacterial Zn2+ metalloprotease 1 and indispensable for NLRP3 inflammasome activation. (2022)
  • Author(s): Kurane, T., Matsunaga, T., Ida, T., Sawada, K., Nishimura, A., Fukui, M., Umemura, M., Nakayama, M., Ohara, N., Matsumoto, S., Akaike, T., Matsuzaki, G., Takaesu, G.
  • Journal Title: FASEB Journal Volume: 36 Issue: 1
  • DOI: 10.1096/fj.202101074rr
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mechanism underlying resveratrol's attenuation of paclitaxel cytotoxicity in human breast cancer cells: Role of the SIRT1-FOXO1-HER3 signaling pathway. (2021)
  • Author(s): Fukui M, Choi HJ, Wang P, Zhu BT.
  • Journal Title: Cancer Treat Res Commun. Volume: 28 Pages: 100386-100386
  • DOI: 10.1016/j.ctarc.2021.100386
  • Peer Reviewed / Open Access