마늘 성분인 Diallyl Disulfide의 유방암 세포주(MCF-7)에 대한 세포사멸 유도기전에 관한 연구
Diallyl Disulfide from Garlic Induces Apoptosis through a Caspase Dependent Pathway in Human Breast Cancer Cell Line, MCF-7
박해린, 서정민, 박경숙, 장항석, 남석진, 배정원, 이경포, 양정현, 구범환,
소속 상세정보
박해린 ( Park Hai-Lin )
포천중문의과대학교 외과학교실
서정민 ( Seo Jeong-Meen )
성균관대학교 의과대학 삼성서울병원 외과학교실
박경숙 ( Park Gyung-Sook )
분자치료연구센터
장항석 ( Jang Hang-Seok )
포천중문의과대학교 외과학교실
남석진 ( Nam Suk-Jin )
성균관대학교 의과대학 삼성서울병원 일반외과
배정원 ( Bae Jung-Won )
고려대학교 의과대학 외과학교실
이경포 ( Lee Kyung-Po )
포천중문의과대학교 외과학교실
양정현 ( Yang Jung-Hyun )
성균관대학교 의과대학 삼성서울병원 일반외과
구범환 ( Koo Bum-Hwan )
고려대학교 의과대학 외과학교실
KMID : 0371320010610020119
Abstract
Purpose
Diallyl disulfide (DADS), an organosulfur compound in garlic, has been reported to be effective in inhibiting the growth of several human tumor cell lines. The aim of this study was to determine whether DADS induced growth inhibition in MCF-7
breast
cancer cell lines and to understand the molecular mechanism by which DADS acts.
Methods
MCF-7 cell lines were incubated with various concentrations of DADS for various time intervals and the cytotoxicity was determined by MTT assay. We examined the changes of intracellular proteins related to apoptosis, such as bcl-2, bax and PARP
in
cells
treated with DADS. To study the expression level of bcl-2 and bax, which serve as modulators of apoptosis, we performed RT-PCR and western blot analysis.
Results
MCF-7 cells treated with DADS led to the suppression of viability and proliferation in both a time and concentration dependent manner. Microscopic observation revealed typical features of apoptosis in the DADS-treated cells, further verified in
nuclear
DAPI staining. Flow cytometry analysis with FITC-annexinV and propidium iodide (PI) demonstrated that the apoptotic cell population with AnnexinV+/PI- increased dramatically from ∼0.8% to ∼75% after 24h exposure to 500μM DADS in MCF-7 cells.
Cellcycle analysis demonstrated that the number of apoptotic cells increased with the increasing time of the DADS treatment. Additionally, thermore, we investigated the effects of DADS on apoptosis related gene expression in MCF-7 cells. PARP
cleavage
was markedly increased in the DADS treated cells with time. This result indicated that DADS induced the caspase-dependent apoptotic pathway. We also found down-regulation of bcl-2, however no significant change of Bax expression was observed
after
DADS
treatment.
Conclusion
Taken together, these results indicate that DADS induces apoptosis by activating a caspase pathway involving the activation of Bcl-2 but not of Bax. Our findings suggest chemotherapeutic potentials of DADS in human breast cancer.
키워드
마늘; 유방암 세포주; 세포사멸; Diallyl disulfide; Garlic; MCF-7 breast cancer cell line; Apoptosis;
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