2011 Fiscal Year Final Research Report
SIRT1, a longevity gene encoded protein, regulates apoptosis of adult T-cell leukemia cells and its inhibition by sirtinol induces apoptosis
| Project/Area Number |
22790921
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Fukuoka University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Keywords | 血液免疫学 / 長寿遺伝子 |
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| Research Abstract |
Adult T-cell leukemia-lymphoma(ATL) is an aggressive peripheral T-cell neoplasm that develops after long-term infection with human T-cell leukemia virus(HTLV-1). SIRT1, a nicotinamide adenine dinucleotide(+)-dependent histone/protein deacetylase, plays a crucial role in various physiological processes, such as aging, metabolism, neurogenesis and apoptosis, owing to its ability to deacetylate numerous substrates, such as histone and NF-κB, which is implicated as an exacerbation factor in ATL. Here, we assessed how SIRT1 is regulated in primary ATL cells and leukemic cell lines. SIRT1 expression in ATL patients was significantly higher than that in healthy controls, especially in the acute type. Sirtinol, a SIRT1 inhibitor, induced significant growth inhibition or apoptosis in cells from ATL patients and leukemic cell lines, especially HTLV-1-related cell lines. Sirtinol-induced apoptosis was mediated by activation of the caspase family and degradation of SIRT1 in the nucleus. Furthermore, SIRT1 knockdown by SIRT1-specific small interfering RNA caused apoptosis via activation of caspase-3 and PARP in MT-2 cells, HTLV-1-related cell line. These results suggest that SIRT1 is a crucial antiapoptotic molecule in ATL cells and that SIRT1 inhibitors may be useful therapeutic agents for leukemia, especially in patients with ATL.
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[Journal Article] Novel Cytotoxic Isolated from Jamaican Hyptis verticillata jacq Induces Apoptosis and Overcomes Multidrug Resistance2011
Author(s)
White Y, Hamada T, Yoshimitsu M, Nakashima M, Hachiman M, Kozako T, et al. White Y, Hamada T, Yoshimitsu M, Nakashima M, Hachiman M, Kozako T, et al.(他5名, 6番目)
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Journal Title
Anticancer Res
Volume: 12
Pages: 4251-7
Peer Reviewed
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