Establishment of cancer stem cell targeting therapy using autophagy inhibitory activity of macrolide antibiotics
| Project/Area Number |
17K15031
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor therapeutics
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | マクロライド / オートファジー / がん / 細胞骨格 |
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| Outline of Final Research Achievements |
This study revealed the intracellular target of azithromycin (AZM) for autophagy inhibition, and clarified one of the mechanisms how AZM inhibited autophagy. Additionally, we compared the autophagy inhibitory effect with other autophagy inhibitors, HCQ and Bafilomycin, and showed in which point AZM disrupted the autophagy. Particularly, unlike HCQ, we showed that AZM did not induce HIF-1a which is an important gene to sustain and promote cancer stem cell ability. Moreover, we also showed that AZM inhibited autophagy in transplanted tumors by oral administration, and suppressed tumor growth with xenograft mice model. These data show that AZM can be a good candidate for cancer therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、がんにおけるオートファジーの様々な役割が明らかとなり、オートファジー阻害薬ががん治療の候補の1つに挙げられているが、実際に臨床で用いることのできるオートファジー阻害薬は1つしか無く、また、副作用が存在することもあり、臨床で用いることのできる新しいオートファジー阻害薬の開発は選択肢を増やす上でも非常に有用であり、望まれていることである。AZMは抗生物質として長年臨床の場で用いられた薬剤であり、また、本研究で明らかとなったAZMのオートファジー阻害効果の詳細は、AZMをオートファジー阻害薬として臨床応用する上での重要な意義を持つと考える。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Amino acid starvation culture condition sensitizes EGFR-expressing cancer cell lines to gefitinib-mediated cytotoxicity by inducing atypical necroptosis.2018
Author(s)
Saito Y, Moriya S, Kazama H, Hirasawa K, Miyahara K, Kokuba H, Hino H, Kikuchi H, Takano N, Hiramoto M, Tsukahara K, Miyazawa K.
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Journal Title
Int J Oncol.
Volume: 52
Pages: 1165-1177
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] BRCA1 degradation in response to mitochondrial damage in breast cancer cells2020
Author(s)
Kana Miyahara, Naoharu Takano, Yumiko Yamada, Hiromi Kazama, Mayumi Tokuhisa, Hirotsugu Hino, Koji Fujita, Edward Barroga, Masaki Hiramoto, Hiroshi Handa, Masahiko Kuroda, Takashi Ishikawa, Keisuke Miyazawa
Organizer
AACR Annual Meeting 2020
Related Report
Int'l Joint Research
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