Induction of apoptosis in human lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins

Büssing, Arndt; Suzart, K; Bergmann, J.; Pfüller, Uwe; Schietzel, M.; Schweizer, Klaus

doi:10.1016/0304-3835(95)04038-2

Cited by 124 publications

(78 citation statements)

References 20 publications

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“…One may speculate that the CD8 + hi counterpart by the expression of a yet undefined galNAc-containing receptor which mediates or facilitates endocytosis of the apoptosis-inducing proteins. This suggestion is corroborated by recent findings that interaction of ML B chains (but not the A chains) with appropriate receptors on lymphocytes increased intracellular Ca 2+ (Bu È ssing et al, 1996a) and inhibited the uptake of [ 3 H]thymidine (Metzner et al, 1987). However, this`activation'-pathway probably does not involve T cell receptor triggering, since T cells did not upregulate CD25 or CD71 expression in response to the MLs (Bu È ssing et al, 1996a + CD62L lo cells to several cytokines, (3) higher susceptibility of these`memory' cells to cell death triggered by the inhibition of protein synthesis, and (4) the presence of a specific`receptor' preferentially expressed on CD8 + CD62L lo cells which mediates subsequently cell death.…”

Section: Discussionsupporting

confidence: 64%

“…The MLs induce an apoptotic cell death in cultured lymphocytes (Bu È ssing et al, 1996a). Within 72 h, the number of Annexin-V + lymphocytes with low PI fluorescence (PI lo ) increased by the addition of ML III, however, even at a final concentration of 3 ng/ml ( (Table 1).…”

Section: Killing Of Cultured Human Lymphocytes By ML Iiimentioning

confidence: 98%

“…However, lectins were also recognised to induce apoptosis in several tumour cell lines, epithelial cells, macrophages, and human lymphocytes (Griffiths et al, 1987;Kim et al, 1993;Janssen et al, 1993;Khan and Waring, 1993;Kulkarni and McCulloch, 1995;Perillo et al, 1995;Bu È ssing et al, 1996a).…”

Section: Introductionmentioning

confidence: 99%

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Selective killing of CD8+ cells with a `memory' phenotype (CD62Llo) by the N-acetyl-D-galactosamine-specific lectin from Viscum album L

1998

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As reported previously by our group, among the toxic proteins from Viscum album L. only the mistletoe lectins (MLs) induce the apoptotic killing pathway in human lymphocytes. Although one may expect a homogenous distribution of carbohydrate domains on cell surface receptors for the carbohydrate binding B chains of the toxic protein, the sensitivity of cells to these B chains obviously differ. Here we report a selective killing of CD8 + CD62L lo cells from healthy individuals by the galNAcspecific ML III (and RCA 60 , which binds to gal and galNAc), while the gal-specific ML I was less effective. This selective killing is not sufficiently explained by protein synthesis inhibition alone, since this subset was not affected by other ribosome inhibiting proteins such as the lectin from Ricinus communis (RCA 120

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Section: Discussionsupporting

confidence: 64%

Section: Killing Of Cultured Human Lymphocytes By ML Iiimentioning

confidence: 98%

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Selective killing of CD8+ cells with a `memory' phenotype (CD62Llo) by the N-acetyl-D-galactosamine-specific lectin from Viscum album L

1998

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“…One obvious explanation is that the precise mode of action of aqueous mistletoe extracts is still unclear. The main therapeutic components of mistletoe extracts are the three mistletoe lectins (MLs) ML-I, -II, -III (Büssing et al, 1996). However, mistletoe extracts contain further numerous low molecular weight compounds such as viscotoxins, polysaccharides, amino acids and phenols, which might show additional or even reverse biological effects on tumour cells (Beuth, 1997).…”

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confidence: 99%

Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model

et al. 2007

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This study investigates the effects of mistletoe lectin-I (ML-I) on melanoma growth and spread in vivo. The human melanoma cell line MV3 was xenografted into severe combined immunodeficient mice and vehicle solution or purified ML-I was administered at 30, 150 and 500 ng per kg body weight (20 mice per group) daily. After 19 days, mice were killed, primary tumours (PTs) and lungs were dissected out, and tumour weights, number of lung metastases (LMs), number of tumour-infiltrating dendritic cells (DCs), and apoptosis rates in the melanoma cells and in the DCs were assessed. A 35% reduction of PT weight (P ¼ 0.03) and a 55% decrease in number of LMs (P ¼ 0.016) were evident for low-dose ML-I (30 ng kg À1 ) treatment but not for higher doses. Mistletoe lectin-I increased apoptosis rates in the melanoma cells of PTs at all doses, while no induction of apoptosis was noted in the LMs. Low-dose ML-I significantly increased the number of DCs infiltrating the PTs (Po0.0001) and protected DCs against apoptosis, while higher doses induced apoptosis in the DCs (Po0.01). Our results demonstrate that low-dose ML-I reduced melanoma growth and number of metastases in vivo, primarily due to immunomodulatory effects.

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“…A direct antitumour effect of mistletoe has been linked to the specific components lectin I -III that can induce apoptosis in various transformed cell lines, in particular in tumour cells of lymphoid origin. (Janssen et al, 1993;Büssing et al, 1996;Hostanska et al, 1996;Bantel et al, 1999). The main effector in mistletoe extracts presumably is the D-galactoside-specific mistletoe lectin I (ML-I).…”

mentioning

confidence: 99%

Recombinant mistletoe lectin induces p53-independent apoptosis in tumour cells and cooperates with ionising radiation

Hostanska¹,

Vuong

Rocha

et al. 2003

Br J Cancer

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Mistletoe extracts are used as alternative cancer treatment in addition to standard chemotherapy and radiation treatment and have an immunostimulatory and pain-relieving effect. A direct antitumour effect of mistletoe extracts against tumour cells of lymphoid origin has been linked to the D-galactoside-specific mistletoe lectin I. In this study, we investigated the cellular effect of bacterially expressed, recombinant mistletoe lectin alone or in combination with ionising radiation in a genetically defined p53-wild-type and p53-deficient E1A/ras-transformed murine tumour cells system. Downregulation of the proliferative activity and cell killing by recombinant mistletoe lectin occurred in a clear dose response (0.1 -1 ng ml À1 ). Induction of apoptosis was p53-independent, but apoptosis-associated factor-1-dependent. Cellular treatment with lectin in combination with ionising radiation resulted in both p53-wild-type and p53-deficient tumour cells in an at least additive, antiproliferative effect and enhanced activation of caspase-3. Combined treatment with ionising radiation and lectin revealed a similar cytotoxic effect in human, p53-mutated adenocarcinoma cells. Thus, recombinant mistletoe lectin alone and in combination with ionising radiation bypasses often prevalent apoptotic deficiencies in treatment-resistant tumour cells.

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Induction of apoptosis in human lymphocytes treated with Viscum album L. is mediated by the mistletoe lectins

Cited by 124 publications

References 20 publications

Selective killing of CD8+ cells with a `memory' phenotype (CD62Llo) by the N-acetyl-D-galactosamine-specific lectin from Viscum album L

Selective killing of CD8+ cells with a `memory' phenotype (CD62Llo) by the N-acetyl-D-galactosamine-specific lectin from Viscum album L

Low-dose mistletoe lectin-I reduces melanoma growth and spread in a scid mouse xenograft model

Recombinant mistletoe lectin induces p53-independent apoptosis in tumour cells and cooperates with ionising radiation

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