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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2007.1
- 수록면
- 47 - 55 (9page)
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Histone deacetylase (HDAC) has been highlighted as one of key players in tumorigenesis and angio-genesis. Recently, several derivatives of psam-maplin (Psams) from a marine sponge have been known to inhibit the HDAC activity, but the molecular mechanism for the inhibition has not fully un-derstood. Here, we explored the mode of action of Psams for the inhibition of HDAC activity in the molecular and cellular level. Among the derivatives, psammaplin A (Psam A) showed the potent inhibitory activity in enzyme assay and anti-proliferation assay with IC50 value of 0.003 and 1 M, respectively. Psam A selectively induced hyper acetylation of histones in the cells, resulting in the upregulation of gelsolin, a well-known HDAC target gene, in a transcriptional level. In addition, reduced Psam A showed a stronger inhibitory activity than that of non-reduced one. Notably, glutathione-depleted cells were not sensi-tive to Psam A, implying that cellular reduction of the compound is responsible for the HDAC inhibition of Psam A after uptake into the cells. Together, these data demonstrate that Psam A could exhibit its activity under the reduced cobe a new natural prodrug targeting HDAC.
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참고문헌 (26)
참고문헌 신청
/ / Powers JC. Design of potent reversible inhibitors for thermolysin. Peptides containing zinc coordinating ligands and their use in affinity chromatography. Biochemistry 1
Batova A / 2002 / The histone deacetylase inhibitor AN-9 has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines 100 : 3319 ~ 3324
Davie JR / 1998 / Covalent modification of histones: expression from chromatin templates 8 : 173 ~ 178
Dhordain P / 1998 / The LAZ3 (BCL06) oncoprotein recruits a SMRT/Msin3A/histone deacetylase containing complex to mediate transcriptional repression 26 : 4645 ~ 4651
Finnin MS / 1999 / Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors 401 : 188 ~ 193
Batova A / 2002 / The histone deacetylase inhibitor AN-9 has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines 100 : 3319 ~ 3324
Davie JR / 1998 / Covalent modification of histones: expression from chromatin templates 8 : 173 ~ 178
Dhordain P / 1998 / The LAZ3 (BCL06) oncoprotein recruits a SMRT/Msin3A/histone deacetylase containing complex to mediate transcriptional repression 26 : 4645 ~ 4651
Finnin MS / 1999 / Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors 401 : 188 ~ 193
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