폐암세포주 A549에 대한 2,5-diamino Benzamide 유도체의 항암효과

Other Titles
Anticancer Activity of 2,5-diamino Benzamide Derivatives in Lung Carcinoma A549 cells
Authors
김완태
Issue Date
2009-06
Awarded Date
2009
Abstract
본 연구에서는 chemical library 스크리닝을 통해 발굴된 항암성 2,5-diamino benzamide 유도체, 즉 5-(2-Chloroacetylamino)-N-cyclopropyl -2-(4-methylpiperidin-1-yl)-benzamide (CACP) 및 5-(2-Chloroacetylamino) -2-(4-methylpiperidin-1-yl)-N-(2-morpholin-4-ylethyl)-benzamide (CAME)의 항암성과 항암기전을 규명하고자 하였다. CACP와 CAME는 농도 의존적으로 폐암 세포주인 A549 세포의 세포증식을 억제하였으나 인간 피부 섬유아 세포에 대해서는 세포증식 억제성이 높지 않았다. CACP와 CAME 처치는 A549 세포의 sub-G1 fraction 세포비율을과 7-AAD 또는 7-AAD 및 annexin V에 염색되는 세포비율을 증가 시켰으며, CAME 및 CACP 처치에 의한 세포자멸사는 Z-VAD를 전처치 함으로서 감소하였다. 또 Western blot 결과에서 CAME 처치에 의해 procaspase 3가 감소하고, PARP 분절은 증가하였으며 이러한 CAME 작용은 Z-VAD를 전 처치한 경우에 차단되었다. 세포자멸사 억제성 단백질로서 XIAP 및 Mcl-1은 CAME 처치에 의해 변화가 없으나 c-FLIP은 CAME 처치에 의해 감소되었다. 또 CAME은 A549 세포에서와 마찬가지로 신장암 세포주인 Caki 세포와 두경부암 세포주인 AMC-HN4 세포의 증식을 현저히 억제하였다. 이상의 결과로 보아 2,5-diamino benzamide 유도체인 CACP와 CAME는 세포에 선택적 독성을 가지면서 caspase 의존성 세포자멸사를 일으키는 새로운 항암성 화합물이라고 생각된다.
Anticancer activity and mechanism of two 2,5-diamino benzamide derivatives, 5-(2-Chloroacetylamino)-N-cyclopropyl-2-(4-methylpiperidin -1-yl)-benzamide (CACP) and 5-(2-Chloroacetylamino)-2-(4-methylpiperidin -1-yl)-N-(2-morpholin-4-ylethyl)-benzamide (CAME) were investigated. CACP and CAME inhibited the growth of A549 cells, whereas they did not significantly inhibit the growth of normal human skin fibroblast. Treatments of A549 cells with CACP or CAME resulted in a markedly increased accumulation of sub-G1 phase cells and cells stained with 7-AAD or 7-AAD and annexin V. CAME also increased activation of procaspase 3 and cleavage of PARP. However, accumulation of sub-G1 phase cells, activation of procaspase 3 and cleavage of PARP were significantly prevented by treatment with z-VAD in the presence of the CAME. These data clearly indicate that CAME-induced apoptosis is associated with caspase activation. CAME down-regulated cFLIP, but it had no effect on expression levels of XIAP and Mcl-1 protein. CAME also inhibited the growth of Caki cells and AMC-HN4 cells as well as A549 cells. Taken together, these findings suggest that two novel 2,5-diamino benzamide derivatives, CACP and CAME, have selective cytotoxicity to cancer cells, and they can induced caspase-dependent apoptosis.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/11710
Appears in Collections:
3. 학위논문 > 1. School of Medicine (의과대학) > 석사
Full Text
http://dcollection.kmu.ac.kr//jsp/common/DcLoOrgPer.jsp?sItemId=000000008144
File in this Item
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE