KMID : 0371320010610020119
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Journal of the Korean Surgical Society 2001 Volume.61 No. 2 p.119 ~ p.129
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Diallyl Disulfide from Garlic Induces Apoptosis through a Caspase Dependent Pathway in Human Breast Cancer Cell Line, MCF-7
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Park Hai-Lin
Seo Jeong-Meen Park Gyung-Sook Jang Hang-Seok Nam Suk-Jin Bae Jung-Won Lee Kyung-Po Yang Jung-Hyun Koo Bum-Hwan
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Abstract
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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 500¥ìM 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.
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KEYWORD
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