Molecularly targeted photodynamic therapy targeting cancer related mRNA G-quadruplex

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K14042
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Bio-related chemistry
• Research Institution: Konan University
• Principal Investigator: MIYOSHI Daisuke 甲南大学, フロンティアサイエンス学部, 教授 (50388758)
• Co-Investigator(Kenkyū-buntansha): 川内 敬子 甲南大学, フロンティアサイエンス学部, 講師 (40434138)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 四重らせん構造 / RNA / NRAS / がん / 光線力学療法 / 分子標的型 / フタロシアニン

Outline of Final Research Achievements

Ras signaling pathways contributes to aggressive phenotypes of cancer cells. The Ras-targeted therapies for cancer therefore has been recognized to be absolutely effective. On the other hand, it is well known that drug developments targeting Ras is very difficult due to structural feature of Ras protein.
In this project, we found that expression of N-Ras was able to be controlled by photo-irradiation with an anionic phthalocyanine, ZnAPC, targeting NRAS mRNA, which forms a G-quadruplex at its 5' UTR region. It was shown that ZnAPC bound G-quadruplex-forming oligonucleotide derived from NRAS mRNA and cleaved it upon photo-irradiation. Consistent with these results, the combination of photo-irradiation and ZnAPC decreased N-Ras expression and drastically reduced cell viability of cancer cells, MCF-7 cells. These results demonstrate that ZnAPC is prominent for a molecular-targeted photodynamic cancer therapy.

Free Research Field

生体関連化学