Yuchae Jung et al
Mol Cells. 2014 Jul;37(7):547-53. doi: 10.14348/molcells.2014.0158. Epub 2014 Jul 31.
Abstract
Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers.Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and TGFβ signaling pathways are key mediators of Z-ajoene’s action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs.We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.
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Forkhead Box Q1 Is a Novel Target of Breast Cancer Stem Cell Inhibition by Diallyl Trisulfide
Su-Hyeong Kim et al J Biol Chem. 2016 Jun 24;291(26):13495-508. doi: 10.1074/jbc.M116.715219. Epub 2016 Apr 29.
Abstract
Diallyl trisulfide (DATS), a metabolic byproduct of garlic, is known to inhibit the growth of breast cancer cells in vitro and in vivo This study demonstrates that DATS targets breast cancer stem cells (bCSC)… In agreement with these results, stable knockdown of FoxQ1 using small hairpin RNA augmented bCSC inhibition by DATS. Expression profiling for cancer stem cell-related genes suggested that FoxQ1 may negatively regulate the expression of Dachshund homolog 1 (DACH1), whose expression is lost in invasive breast cancer. Chromatin immunoprecipitation confirmed recruitment of FoxQ1 at the DACH1 promoter. Moreover, inducible expression of DACH1 augmented DATS-mediated inhibition of bCSC. Expression of FoxQ1 protein was significantly higher in triple-negative breast cancer cases compared with normal mammary tissues. Moreover, an inverse association was observed between FoxQ1 and DACH1 gene expression in breast cancer cell lines and tumors. DATS administration inhibited ALDH1 activity in vivo in SUM159 xenografts. These results indicate that FoxQ1 is a novel target of bCSC inhibition by DATS.
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Stimulation of cell growth and proliferation in NIH-3T3 cells by onion and garlic oils
J T Zelikoff 1 ,Cell Biol Toxicol. 1986 Sep;2(3):369-78. doi: 10.1007/BF00121852.
Abstract
Onion and garlic oil were seen to shorten the cell-doubling time and stimulate the growth and proliferation of NIH-3T3 cells. Following treatment with either onion or garlic oil, an increase in the growth rate and almost a 2-fold increase in cell number over the control was observed within a 24-hour period. Phorbol myristate acetate when given simultaneously with either oil appeared to nullify both effects. Following exposure to low doses (less than 10 micrograms/ml) of either oil, an increase in cell survival, not seen with the oil control tricaprylin, was observed following a 5-day exposure period. At higher concentrations cell survival decreased proportionately in all cases. The appearance of multinucleated cells, which increased with dose and time, was also observed following treatment with both garlic and onion oil.
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Cancer Chemother Pharmacol.2018 Jun;81(6):969-977. doi: 10.1007/s00280-018-3565-0. Epub 2018 Mar 29.
Qi Zhang 1 Cancer Chemother Pharmacol.2018 Jun;81(6):969-977. doi: 10.1007/s00280-018-3565-0. Epub 2018 Mar 29.
Abstract
Purpose: Cancer stem cells (CSCs) are responsible for colorectal cancer (CRC) initiation, growth, and metastasis. Garlic-derived organosulfur compound diallyl trisulfide (DATS) possesses cancer suppressive properties. Wnt/β-catenin signaling is a key target for CSCs inhibition. However, the interventional effect of DATS on colorectal CSCs has not been clarified. We aimed to illustrate the regulation of Wnt/β-catenin in DATS-induced colorectal CSCs inhibition.
Conclusions: Wnt/β-catenin pathway mediates DATS-induced colorectal CSCs suppression. These findings support the use of DATS for targeting colorectal CSCs.
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Diallyl Trisulfide inhibits breast cancer stem cells via suppression of Wnt/β-catenin pathway
Xiaoting Li 1J Cell Biochem. 2018 May;119(5):4134-4141. doi: 10.1002/jcb.26613. Epub 2018 Jan 22.
Abstract
Cancer stem cells (CSCs) play a central role in the development of breast cancer. The canonical Wnt/β-catenin signal pathway is critical for maintaining CSCs characteristics. Diallyl trisulfide (DATS), a natural organosulfur compound from the garlic, exhibits effective antitumor properties. However, the role of DATS in regulating breast CSCs activity and the underlying molecular mechanisms remain obscure. In the present study, we reported that DATS efficiently inhibited the viability of breast CSCs as evidenced by reducing turmorspheres formation, decreasing the expression of breast CSCs markers (CD44, ALDH1A1, Nanog, and Oct4), as well as inhibiting proliferation and inducing apoptosis. Furthermore, we showed that DATS downregulated the activity of Wnt/β-catenin pathway, while LiCl-triggered Wnt/β-catenin activation diminished DATS inhibition on breast CSCs. Taken together, our results illustrated that DATS suppressed breast CSCs through inhibiting Wnt/β-catenin pathway activation.These novel findings could provide new insights into the molecular mechanisms of breast CSCs regulation as well as its target intervention and might provide new strategies for preventing and treating breast cancers.
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Mistletoe and Garlic Extracts as Polyurethane Carriers – A Possible Remedy for Choroidal Melanoma
Melania F Munteanu 1 Curr Drug Deliv. 2017;14(8):1178-1188. doi: 10.2174/1567201814666170126113231.
Background: Melanoma is known as the most dangerous form of skin cancer; whereas the malignant choroidal melanoma is an orphan disease known as the most common primary intraocular malignancy in adults. Literature suggests that the consumption of garlic and mistletoe leads to a reduced risk of developing cancer.
Conclusion: Sterile eye drops solutions based on polymer microstructures containing garlic or mistletoe extracts were obtained; the sample based on garlic extracts may be used in the pharmaceutical field as drug carrier with an antiproliferative effect which occurs after a prolong period.
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Cancer Biol Ther. 2009 Nov;8(22):2175-85. doi: 10.4161/cbt.8.22.9882. Epub 2009 Nov 22.
Garlic constituent diallyl trisulfide induced apoptosis in MCF7 human breast cancer cells
Ahmed Malki 1 , Cancer Biol Ther. 2009 Nov;8(22):2175-85. doi: 10.4161/cbt.8.22.9882. Epub 2009 Nov 22.
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 (diallyl trisulfide) administration might offer a novel strategy for the treatment of human breast cancer.