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Published on: June 9, 2023
Garlic constituent diallyl trisulfide induced apoptosis in MCF7 human breast cancer cells
Ahmed Malki1, Muhammad El-Saadani, Ahmed S Sultan
1Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.
Abstract:
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.
Insights
Garlic compound diallyl trisulfide (DATS) effectively suppresses human breast cancer cell growth and induces apoptosis. DATS shows promise as a novel therapeutic strategy for breast cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Chemoprevention
Background:
- Breast cancer is a leading cause of cancer-related deaths in women.
- Garlic-derived organosulfur compounds (OSCs) exhibit potent antitumor effects.
- The specific mechanisms of OSCs in cancer prevention require further investigation.
Purpose of the Study:
- To investigate the effects of diallyl trisulfide (DATS) on human breast cancer cell lines.
- To compare DATS efficacy on MCF-7 (cancerous) and MCF-12a (non-tumorigenic) cells.
- To elucidate the molecular mechanisms underlying DATS-induced cell death.
Main Methods:
- MTT assay, clonogenic survival assay, ELISA, TUNEL assay, immunofluorescence, flow cytometry.
- Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis.
- Assessment of cell cycle progression, apoptosis, and protein expression levels.
Main Results:
- DATS suppressed the viability of both MCF-7 and MCF-12a cells by inducing G2/M phase arrest and apoptosis.
- Apoptosis was more pronounced in MCF-7 cells, correlating with elevated cyclin B1 levels.
- DATS modulated the expression of key proteins, including upregulation of FAS, cyclin D1, Bax, and p53, and downregulation of Akt and Bcl-2.
Conclusions:
- DATS effectively inhibits breast cancer cell proliferation and induces apoptosis through specific molecular pathways.
- DATS demonstrates differential effects on cancerous versus non-tumorigenic cells.
- DATS represents a potential novel therapeutic agent for human breast cancer treatment.
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