Garlic constituent diallyl trisulfide induced apoptosis in MCF7 human breast cancer cells.
Identification of agents that are nontoxic but can delay onset and/or progression of breast cancer, which is the main leading cause of cancer-related deaths among women, is highly desirable. Garlic-derived organosulfur compounds (OSCs) have highly effective antitumor effects, but the mechanism has yet to be investigated. The aim of the present study was undertaken to examine the effect of diallyl trisulfide (DATS), a promising cancer chemopreventive constituent of garlic, on growth of two cell lines respectively, MCF-7 human breast cancer cells and nontumorigenic MCF-12a mammary epithelial cells. The effects of DATS were examined by MTT assay, clonogenic survival assay, ELISA based apoptotic assay, TUNEL assay, immunofluoresence staining, flow Cytometry, RT-PCR and western blot analysis. Garlic constituent diallyl trisulfide (DATS) suppresses viability of cultured MCF-7 and MCF-12a cells respectively by decreasing the percent of cells in G(2)/M and inducing apoptotic cell death. DATS-induced apoptosis was markedly elevated in MCF-7 cells compared with MCF-12a cells and this was correlated with elevated levels of cyclin B1. The results from semi-quantitative and real-time RT-PCR indicated that DATS-enhanced the expression levels of FAS and cyclin D1, but in contrast, downregulated the expression levels of Akt and Bcl-2. Furthermore, the DATS-induced apoptosis was correlated with induction of pro-apoptotic Bax protein and p53 protein expression was upregulated and translocation to nucleus in MCF-7 cells. Together, the results of the present study show, for the first time, that DATS administration might offer a novel strategy for the treatment of human breast cancer.
Malki
Ahmed
A
Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.
El-Saadani
Muhammad
M
Sultan
Ahmed S
AS
D000230:Adenocarcinoma / Q000473:pathology*; D000498:Allyl Compounds / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D001940:Breast / Q000166:cytology; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D005737:Garlic / Q000737:chemistry*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013440:Sulfides / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D013440:Sulfides; C042577:diallyl trisulfide