Anticancer activity and mechanism of action of histone H2A-derived peptides = Histone H2A 유래 펩타이드의 항암 활성 및 작용 기작

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Buforin IIb, a synthetic analog of antimicrobial peptide buforin II, is a cell-penetrating peptide with potent antimicrobial activity against various microorganisms. Buforin IIb showed cytotoxicity toward 62 cancer cell lines with $IC_{50}$ values in the ranges of 6-24 ug/ml, whereas normal cells were insensitive to buforin IIb up to 200㎍/ml. Buforin IIb rapidly penetrated the cell membrane without cell lysis and accumulated in the nucleus of the cancer cells. Exogenous gangliosides decreased cytotoxicity and cellular entry of buforin IIb in cancer cells. Moreover, the depletion of cell surface gangliosides or sialic acids reduced buforin IIb-induced cytotoxicity. These results indicate cell surface gangliosides or sialic acids might be the binding target of buforin IIb. Cancer cells treated with buforin IIb manifested apoptotic changes, including DNA fragmentation, annexin V staining, and activation of caspases and PARP. Buforin IIb induced mitochondria-dependent apoptosis, as evidenced by activation of caspase-9 and cytochrome c release into cytosol. Gel retardation and Western blot analysis showed that buforin IIb can also bind to intracellular macromolecules, such as DNA, RNA, or heat shock proteins. Two-dimensional gel electrophoresis and mass spectrometric analysis showed that chaperones and heat shock proteins were over-expressed in buforin IIb-treated cells. In vivo analysis of anticancer activity showed that buforin IIb reduced the volume of fibrosarcoma masses in p53-deficient mice and killed almost all of the tumor cells. In addition, buforin IIb showed remarkable tumor suppressing activity above the concentration of 10 mg/Kg in a mouse tumor xenograft model.
Advisors
Kim, Sun-Changresearcher김선창researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2004
Identifier
240504/325007  / 000985302
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2004.2, [ vi, 80 p. ]

Keywords

H19; APOPTOSIS; GANGLIOSIDES; CELL-PENETRATING; ANTICANCER PEPTIDE; IMPRINTING CONTROL REGION (ICR); 각인 조절 부위; 에이치19; 세포사멸 2; 갱글리오사이드; 세포투과; 항암펩타이드

URI
http://hdl.handle.net/10203/27565
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=240504&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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