Elucidatinon of the mechanism by wihch fatty acids alter the malignant features of ovarian cancer int terms of palmitoylation.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K18166
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Kyoto University
• Principal Investigator: Yamanoi Koji 京都大学, 医学研究科, 助教 (70868075)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 飽和脂肪酸 / ステアリン酸 / DNA障害 / アシル化

Outline of Final Research Achievements

The effects of palmitic acid, oleic acid, and stearic acid, which are long-chain fatty acids abundant in the body, on several ovarian cancer cell lines were examined in vitro, and stearic acid was found to apparently inhibit several ovarian cancer cell lines. This effect was also confirmed in vivo. Furthermore, inhibition of desaturating enzyme ,SCD, markedly enhanced the tumor growth inhibitory effect in vivo.
Mechanistically, DNA damage is clearly observed by exposure of stearic acid. Furthermore, it is also suggested that endoplasmic reticulum stress can be induced. Among these two mechanisms, DNA damage seems to be the main factor. LC-MS analysis showed that acylation of ribosomal proteins by stearic acid can be involved. We would like to elucidate the mechanism by which acylation of ribosomal proteins by stearic acid is involved in DNA damage process.

Free Research Field

産科婦人科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、長鎖脂肪酸の中でもステアリン酸が特に、卵巣癌細胞に対する強い細胞障害を及ぼすことが初めて明らかになった。in vivoでも効果を確認したのは本研究が初めてである。特にステアリン酸リッチな食事による細胞増殖抑制効果は、大きな社会的意義を持つと考えられる。
ステアリン酸はパーム脂など日常の食事にふんだんに含まれるものであり、これを軸とした食事治療は十分導入が現実的に検討できる。癌治療の中で初めて、具体的なエビデンスを持った食事治療を提唱する、一つの根拠になると考えられる。メカニズムの探索をさらに行うことで、ステアリン酸に着目した食事療法の可能性をさらに拡げたいと考えている。