Induction of apoptosis in tumor cells by naturally occurring sulfur-containing compounds

Wu, Xuehang; Kassie, Fekadu; Mersch-Sundermann, Volker

doi:10.1016/j.mrrev.2004.11.001

Cited by 130 publications

(99 citation statements)

References 135 publications

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“…Sulforaphane dosedependently inhibited the proliferation of HMEC-1 cells after an incubation time of 72 hours. By comparison with additional cancer cell lines, we confirmed earlier reports indicating that the antiproliferative activity of sulforaphane was not specific for endothelial cells (59). By flow cytometry, we observed a time-and concentrationdependent increase in a sub-G 1 peak indicative of apoptosis induction in HMEC-1 cells (Fig.…”

Section: Discussionsupporting

confidence: 90%

Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention

Bertl

Bartsch

Gerhäuser

2006

Molecular Cancer Therapeutics

164

124

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Sulforaphane, an aliphatic isothiocyanate, is a known cancer chemopreventive agent. Aiming to investigate antiangiogenic potential of sulforaphane, we here report a potent decrease of newly formed microcapillaries in a human in vitro antiangiogenesis model, with an IC 50 of 0.08 Mmol/L. The effects of sulforaphane on endothelial cell functions essential for angiogenesis were investigated in HMEC-1, an immortalized human microvascular endothelial cell line. Molecular signaling pathways leading to activation of endothelial cell proliferation and degradation of the basement membrane were analyzed by reverse transcription-PCR. Sulforaphane showed time-and concentration-dependent inhibitory effects on hypoxiainduced mRNA expression of vascular endothelial growth factor and two angiogenesis-associated transcription factors, hypoxia-inducible factor-1A and c-Myc, in a concentration range of 0.8 to 25 Mmol/L. In addition, the expression of the vascular endothelial growth factor receptor KDR/flk-1 was inhibited by sulforaphane at the transcriptional level. Sulforaphane could also affect basement membrane integrity, as it suppressed transcription of the predominant endothelial collagenase matrix metalloproteinase-2 and its tissue inhibitor of metalloproteinase-2. Migration of HMEC-1 cells in a wound healing assay was effectively prevented by sulforaphane at submicromolar concentrations, and we determined an IC 50 of 0.69 Mmol/L. In addition, within 6 hours of incubation, sulforaphane inhibited tube formation of HMEC-1 cells on basement membrane matrix at 0.1, 1, and 10 Mmol/L concentrations. These effects were not due to inhibition of HMEC-1 cell proliferation; however, after 72 hours of incubation, sulforaphane nonselectively reduced HMEC-1 cell growth with an IC 50 of 11.3 Mmol/L. In conclusion, we have shown that sulforaphane interferes with all essential steps of neovascularization from proangiogenic signaling and basement membrane integrity to endothelial cell proliferation, migration, and tube formation. These novel antiangiogenic activities of sulforaphane are likely to contribute to its cancer chemopreventive and therapeutic potential. [Mol Cancer Ther 2006;5(3):575 -85]

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Section: Discussionsupporting

confidence: 90%

Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention

Bertl

Bartsch

Gerhäuser

2006

Molecular Cancer Therapeutics

164

124

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“…Depending on conditions of its cultivation, garlic can contain at least 33 different organosulfur compounds in addition to amino acids, vitamins, and micronutrients. The allyl sulfur compounds formed by enzymatic activity when garlic is minced or crushed, such as allicin, water-soluble Sallylmercaptocysteine (SAMC) and S-allylcysteine (SAC), and oil-soluble diallyl disulfide (DADS) and diallyl sulfide (DAS), probably account for the majority of these anticancer effects (4,5).…”

Section: Introductionmentioning

confidence: 99%

Effects of a series of organosulfur compounds on mitotic arrest and induction of apoptosis in colon cancer cells

Xiao

Pinto²,

Gundersen³

et al. 2005

Molecular Cancer Therapeutics

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We previously reported that the garlic-derived compound S-allylmercaptocysteine (SAMC) causes growth inhibition, mitotic arrest, and induction of apoptosis in SW480 human colon cancer cells by inducing microtubule depolymerization and c-Jun NH 2 terminus kinase-1 activation. In the present study, we compared the aforementioned effects of SAMC to those of a series of garlic-derived and other organosulfur compounds. Among the 10 compounds tested, only SAMC, diallyl disulfide (DADS), and S-trityl-Lcysteine (trityl-cys) cause significant inhibition of cell growth with IC 50 values of 150, 56, and 0.9 Mmol/L, respectively. These three compounds also induce G 2 -M cell cycle arrest and apoptosis. Further studies reveal that, like SAMC, the garlic-derived compound DADS exerts antiproliferative effects by binding directly to tubulin and disrupting the microtubule assembly, thus arresting cells in mitosis and triggering mitochondriamediated signaling pathways that lead to apoptosis. However, the synthetic compound trityl-cys exerts its effect on M-phase arrest and growth inhibition by mechanisms that involve spindle impairment but do not involve disruption of microtubule structure or dynamics. Furthermore, trityl-cys does not induce marked loss of mitochondrial membrane potential or release of cytochrome c, but it does induce caspase-3 activation and poly(ADP-ribose) polymerase cleavage. Structure-function analysis suggests that both the allyl and the disulfide moieties are important features for the antiproliferative effects of SAMC and DADS. These findings may be useful in the identification, synthesis, and development of organosulfur compounds that have anticancer activity. [Mol Cancer Ther 2005;4(9):1388 -98]

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“…These findings were similar to those obtained by Khan and Sultana,31 who recorded that Nigella sativa is a potent chemopreventive agent and suppresses Fe-NTA-induced oxidative stress, hyperproliferative response and renal carcinogenesis in Wistar rats. Garlic and its allyl sulfur may exert their protective effects on carcinogenesis in animal and in vitro by several mechanisms, including inhibition of carcinogen-induced DNA adduct formation, 32 blockage of cell growth, blockage of cell proliferation, and blockage of angiogenesis, 33 induction of differentiation and/or apoptosis, 5,34 enhancement of carcinogen-detoxifying enzymes, 35 and/or suppression of carcinogenactivating enzymes, 36 inhibition of cyclooxygenase-2 expression, 37 scavenging carcinogeninduced free radicals, 38,39 and inhibition of lipid peroxidation. 39,40 Another possible mechanism of cancer prevention and suppression of cancer progression is immune enhancement by garlic, 9 and Nigella sativa, 21 and these agreed with our hematologic and histopathological findings.…”

Section: Articlementioning

confidence: 99%

Ultrapathological evaluation of the anticancer effect of blackseed (Nigella sativa) and garlic (Allium sativum) in mice

Nouh

2013

Vet Sci Develop

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In this experimental work, 120 virgin female mice (body weight 40±10 gm) were divided into 6 equal groups. Mice in Group 1 served as a control. Mice in Groups 2 and 3 were fed on a basal diet provided with 100 mg/kg b.wt from each of blackseed (Nigella sativa) and garlic (Allium sativum), respectively, for one month. Mice in Group 4 were inoculated subcutanously (S/C) with Ehrlich tumor cells after one month from the start of the experiment. Mice in Groups 5 and 6 were treated similarly to those in Groups 3 and 4, respectively, for one month and then immediately inoculated S/C with Ehrlich tumor cells (ETC, 0

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Induction of apoptosis in tumor cells by naturally occurring sulfur-containing compounds

Cited by 130 publications

References 135 publications

Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention

Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention

Effects of a series of organosulfur compounds on mitotic arrest and induction of apoptosis in colon cancer cells

Ultrapathological evaluation of the anticancer effect of blackseed (Nigella sativa) and garlic (Allium sativum) in mice

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