Anti-tumor effect achieved by effective induction of ferroptosis utilizing non-transferrin-bound iron
| Project/Area Number |
18K08347
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
IKUTA KATSUYA 旭川医科大学, 医学部, 客員教授 (00396376)
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| Co-Investigator(Kenkyū-buntansha) |
田中 宏樹 旭川医科大学, 医学部, 助教 (70596155)
土岐 康通 旭川医科大学, 医学部, 特任助教 (90596280)
齋藤 豪志 旭川医科大学, 大学病院, 医員 (80837930)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | フェロトーシス / 抗腫瘍効果 / 非トランスフェリン結合鉄（NTBI） / 鉄 / labile plasma iron (LPI) / 非トランスフェリン結合鉄 |
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| Outline of Final Research Achievements |
The present study was performed to elucidate the precise mechanisms of iron involvement for ferroptosis by using molecular biological techniques and also to elucidate the effective methods for inducing ferroptosis by iron modulation. Various cell lines derived from such as hepatocellular carcinoma, hematological malignancies, pancreas cancers showed ferroptosis by ferroptosis inducing reagent erastin. The inhibitory effect for cell growth by erastin was increased by adding iron to cell culture medium. Especially, non-transferrin-bound iron (NTBI) and labile plasma iron (LPI) seemed to cause ferroptosis effectively than transferrin-bound iron. We consider that the present data showed the possibility of effective induction of ferroptosis by iron modulation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、肝癌、血液腫瘍、膵癌など様々な腫瘍細胞において、新しい細胞死フェロトーシスが起こることが確認され、さらに誘導物質に少量の鉄負荷を行うと、より効率的に起こることが示された。加えて、トランスフェリンと結合していない非トランスフェリン結合鉄（NTBI）やNTBIによる酸化能labile plasma iron (LPI)が特に効率的に腫瘍細胞にフェロトーシスを惹起する可能性も見出し、指標としての意義も示唆された。各種難治性腫瘍に対する既存薬物とは全く異なる新規の治療アプローチに繋がる可能性が示され、今後の基礎および臨床研究にも寄与できる基盤となる意義深い結果を得られたと考えている。
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Report
(4 results)
Research Products
(35 results)
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[Journal Article] Long-term phlebotomy successfully alleviated hepatic iron accumulation in a ferroportin disease patient with a mutation in SLC40A1: A case report.2021
Author(s)
Nishina S, Tomiyama Y, Ikuta K, Tatsumi Y, Toki Y, Kato A, Kato K, Yoshioka N, Sasaki K, Hara Y, Hino K.
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Journal Title
BMC Gastroenterology
Volume: 21(1)
Issue: 1
Pages: 111-111
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Type 4B hereditary hemochromatosis due to heterozygous p.D157A mutation in SLC40A1 complicated with hypopituitarism.2021
Author(s)
Honma Y, Karasuyama T, Kumamoto K, Shimajiri S, Toki Y, Tatsumi Y, Sumida K, Koikawa K, Morino K, Oe S, Miyagawa K, Yamasaki M, Shibata M, Abe S, Ikuta K, Hayashi H, Harada M.
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Journal Title
Medical Molecular Morphology
Volume: 54(1)
Issue: 1
Pages: 60-67
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of Heterozygous p.Y150C and p.V274M Mutations in the HJV Gene in a Japanese Patient With a Mild Phenotype of Juvenile Hemochromatosis: A Case Report2020
Author(s)
Kawaguchi T, Ikuta K, Tatsumi Y, Toki Y, Hayashi H, Tonan T, Ohtake T, Hoshino S, Naito M, Kato K, Okumura T, Torimura T.
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Journal Title
Hepatology Research
Volume: 50 (1)
Issue: 1
Pages: 144-150
DOI
Related Report
Peer Reviewed
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[Journal Article] Successful Treatment of Nivolumab-related Cholangitis with Prednisolone: A Case Report and Review of the Literature2019
Author(s)
Sawada K, Shonaka T, Nishikawa Y, Hasegawa K, Hayashi H, Hasebe T, Nakajima S, Ikuta K, Fujiya M, Furukawa H, Okumura T.
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Journal Title
Internal Medicine
Volume: 58
Issue: 12
Pages: 1747-1752
DOI
NAID
ISSN
0918-2918, 1349-7235
Year and Date
2019-06-15
Related Report
Peer Reviewed / Open Access
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[Journal Article] Autofluorescence Imaging Reflects the Nuclear Enlargement of Tumor Cells as well as the Cell Proliferation Ability and Aberrant Status of the p53, Ki-67, and p16 Genes in Colon Neoplasms2019
Author(s)
Moriichi K, Fujiya M, Kobayashi Y, Murakami Y, Iwama T, Kunogi T, Sasaki T, Ijiri M, Takahashi K, Tanaka K, Sakatani A, Ando K, Nomura Y, Ueno N, Kashima S, Ikuta K, Tanabe H, Mizukami Y, Saitoh Y, Okumura T.
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Journal Title
Molecules
Volume: 24
Issue: 6
Pages: 1106-1106
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Hereditary Hemochromatosis-related gene mutation analysis in Japan.2019
Author(s)
Saito T, Toki Y, Tamamura N, Funayama T, Igarashi S, Ishioh M, Hatayama M, Shindo M, Ikuta K, Torimoto Y, Tatsumi Y, Kato A, Hayashi H, Kato K, Okumura T.
Organizer
第81回日本血液学会学術集会
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