2019 Fiscal Year Final Research Report
Discovery of natural anticancer agents that inhibit cancer cells' tolerance to nutrition starvation and elucidation of their molecular mechanisms
| Project/Area Number |
16K08319
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Drug development chemistry
|
|---|
| Research Institution | University of Toyama |
|---|
Principal Investigator |
Awale Suresh 富山大学, 学術研究部薬学・和漢系, 准教授 (00377243)
|
|---|
| Project Period (FY) |
2016-04-01 – 2020-03-31
|
| Keywords | Pancreatic cancer / Drug discovery / PANC-1 / Antiausterity agent / metabolomics / molecular mechanism / natural products |
|---|
| Outline of Final Research Achievements |
The project aimed to discover novel anti-cancer agents by employing an anti-austerity strategy and to elucidate the mechanism of action through protein and metabolome analysis. Extensive investigation on the anti-cancer activity of the active principals from the medicinal plants Ferula hezarlalehzarica, Ancistrocladus abbreviatus, Calotropis gigantea, Artemisia vulgaris, Anneslea fragrans, Ancistrocladus ealaensis, Bosenbergia pandurata、Uvaria dac, Chamaecyparis obtusa, Citrus hystrix, Derris scandens, Callistemon citrinus has been investigated. The investigation of the mechanism of action of the selected novel anticancer agents was accomplished. In particular, the novel compound, a 5,8-linked naphthyl isoquinoline alkaloid Ancistrolikokine E3 was discovered as a promising anticancer agent that eliminates cancer cells' tolerance to nutrient starvation. Ancistrolikokine E3 was found to inhibit Akt/mTOR/Autophagy Signaling Pathway and causes pancreatic cancer cell death.
|
| Free Research Field |
創薬、ケミカルバイオロジー
|
| Academic Significance and Societal Importance of the Research Achievements |
本プ ロジェクトでは、査読付きの国際学術誌に27本の論文を発表し、国際招待講演4件、国際会議8件を含む46件の学会発表を行った。新規化合物Ancistrolikokine E3 は、栄養飢餓に対するがん細胞の耐性を除去する有望な抗がん剤であることが発見され た。この発見は、ACS(米国化学協会) により重要な発見として選ばれ、世界中の数千のニュースメディアにプレスリリースされた。約130の国際的なニュースメディアがこの発見を取り上げた。このプロジェクトで発見された化合物は、抗がん剤開発の潜在的な種を表しています。
|
