Structure–activity studies on the anti-proliferation activity of ajoene analogues in WHCO1 oesophageal cancer cells

Kaschula, Catherine H.; Hunter, Roger; Stellenboom, Nashia; Caira, Mino R.; Winks, Susan; Ogunleye, Thozama; Richards, Philip I.; Cotton, Jonathan; Zilbeyaz, Kani; Wang, Yabing; Siyo, Vuyolwethu; Ngarande, Ellen; Parker, M. Iqbal

doi:10.1016/j.ejmech.2012.01.058

Cited by 56 publications

(64 citation statements)

References 54 publications

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“…In support of this, the disulfide bond in ajoene was found to be important for both anti-microbial and anti-cancer activities where removal of the disulfide to the sulfide rendered the analog inactive in both cases [16, 17]. Disulfides and polysulfides can be considered as thiol oxidising agents, able to thiolate cysteine residues in proteins to form mixed disulfides.…”

Section: The Organosulfur Compounds In Crushed Garlicmentioning

confidence: 99%

The Immunomodulation and Anti-Inflammatory Effects of Garlic Organosulfur Compounds in Cancer Chemoprevention

Schäfer

Kaschula

2014

ACAMC

160

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Garlic (Allium sativum) has been used for centuries as a prophylactic and therapeutic medicinal agent. Importantly, garlic has been suggested to have both cancer-preventive potential as well as significant enhancing effects on the immune system. While these observations are supported experimentally both in vitro and in vivo, the impact of garlic in assisting the immune system in the prevention of cancer still lacks experimental confirmation. Studies addressing the immunomodulatory effects of garlic reveal conflicting data as to pro- or anti-inflammatory responses depending on the particular experimental set-ups and the garlic preparation used (i.e. garlic extract versus chemically pure garlic compounds). Here we provide an overview of the chemistry of the major garlic organosulfur compounds, summarize the current understanding and propose a link between the immunomodulating activity of garlic and the prevention of cancer. We hypothesize that garlic rather elicits anti-inflammatory and anti-oxidative responses that aid in priming the organism towards eradication of an emerging tumor.

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Section: The Organosulfur Compounds In Crushed Garlicmentioning

confidence: 99%

The Immunomodulation and Anti-Inflammatory Effects of Garlic Organosulfur Compounds in Cancer Chemoprevention

Schäfer

Kaschula

2014

ACAMC

160

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“…It has been reported that Z-ajoene functions as an antioxidant agent and may be a potent antithrombotic agent (Kaschula et al, 2012). It has also been reported that Z-ajoene has anti-proliferative effects on several cancer cells at high concentration (Li= et al, 2002;Taylor=et al, 2006).…”

Section: Introductionmentioning

confidence: 98%

“…Z-ajoene was first isolated from processed garlic in an E/Zmixture (Block et al, 1984;Kaschula=et al, 2012). It has been reported that Z-ajoene functions as an antioxidant agent and may be a potent antithrombotic agent (Kaschula et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Systemic Approaches Identify a Garlic-Derived Chemical, Z-ajoene, as a Glioblastoma Multiforme Cancer Stem Cell-Specific Targeting Agent

Jung¹,

Park²,

Zhao³

et al. 2014

Molecules and Cells

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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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“…E-ajoene and Epropyl-ajoene were synthesized as described previously (24). Reagents for cell culture (culture medium, fetal bovine serum, and antibiotics) were purchased from Life Technologies/ Thermo Fisher Scientific (Waltham, MA).…”

Section: Methodsmentioning

confidence: 99%

Forkhead Box Q1 Is a Novel Target of Breast Cancer Stem Cell Inhibition by Diallyl Trisulfide

Kim

Kaschula

Priedigkeit

et al. 2016

Journal of Biological Chemistry

Self Cite

111

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Structure–activity studies on the anti-proliferation activity of ajoene analogues in WHCO1 oesophageal cancer cells

Cited by 56 publications

References 54 publications

The Immunomodulation and Anti-Inflammatory Effects of Garlic Organosulfur Compounds in Cancer Chemoprevention

The Immunomodulation and Anti-Inflammatory Effects of Garlic Organosulfur Compounds in Cancer Chemoprevention

Systemic Approaches Identify a Garlic-Derived Chemical, Z-ajoene, as a Glioblastoma Multiforme Cancer Stem Cell-Specific Targeting Agent

Forkhead Box Q1 Is a Novel Target of Breast Cancer Stem Cell Inhibition by Diallyl Trisulfide

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