Apoptosis induced by diallyl disulfide in human breast cancer cell line MCF-7.
OBJECTIVE
To investigate the effect of diallyl disulfide (DADS), a component of garlic, on apoptosis in human mammary cancer cell line (MCF-7) and its mechanisms.


METHODS
Cytotoxicity was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assays. Morphology of apoptotic cells was detected by acridine orange and ethidium bromide staining. Apoptotic cells stained with propidium iodide were examined using flow cytometry. Protein levels were detected by Western blot analysis.


RESULTS
DADS inhibited the proliferation of MCF-7 cells and induced the apoptotic ratio to increase rapidly. Cleavage of the caspase-3 and caspase-3 substrate poly(ADP-ribose) polymerase was observed in MCF-7 cells after 24 h of treatment with DADS. When the MCF-7 cells were treated with 200 micromol x L DADS, the stress-activated protein kinase extracellular signal-regulated kinase (ERK), a mitogen-activated protein kinase, was inhibited after 6 h; c-Jun N-terminal kinase (JNK), that is stress-activated protein kinase (SAPK), and p38 mitogen-activated protein kinase were activated after 6 h.


CONCLUSIONS
These results suggest that DADS both inhibits the proliferation of MCF-7 cells and induces apoptosis of MCF-7 cells. The mechanisms may include the inhibition of ERK and the activation of the SAPK/JNK and p38 pathways.
Lei
Xiao-yong
XY
Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, China. lei_xiaoyong@yahoo.com.cn
Yao
Shu-qiong
SQ
Zu
Xu-yu
XY
Huang
Ze-xiang
ZX
Liu
Li-juan
LJ
Zhong
Miao
M
Zhu
Bing-yang
BY
Tang
Sheng-song
SS
Liao
Duan-fang
DF
D000498:Allyl Compounds / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D005260:Female; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000498:Allyl Compounds; D000972:Antineoplastic Agents, Phytogenic; D013440:Sulfides; D016159:Tumor Suppressor Protein p53; C038491:allyl sulfide; D011065:Poly(ADP-ribose) Polymerases; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D053148:Caspase 3