7 research outputs found
Suppression of growth of tumour cell lines in vitro and tumours in vivo by mistletoe lectins
A variety of studies have shown that
incubation of different tumour cell lines with mistletoe
lectins (MLs) in vitro has a marked cytotoxic effect. In
the concentration range of low cytotoxicity cell death
induced by ML-I is quantitatively due to apoptotic
processes. The first events observed being membrane
perforation and protusions. Simultaneous treatment of
certain tumour cells with MLs rendered them more
sensitive to induction of apoptosis by TNFa. The
immunomodulatory activity of ML-I was investigated by
measuring cytokine release and the results confirmed
that cytokine induction by the lectin is regulated at the
transcriptional level. ML-I has been shown to potentiate
the effect of chemotherapeutic drugs. In addition to an in
vitro effect a number of workers have demonstrated that
MLs suppress tumour growth in vivo. Mistletoe lectins
have been administered to animals locally to the tumour,
systemic, subcutaneously or by the oral route via the
diet. In many cases apoptosis was observed in the
tumour and instances where complete tumour ablation
has occurred have been reported. It has been
hypothesized that the anticancer efficacy of tumour
necrosis factor-alpha (TNFa) is potentiated by MLs
isolated from both European and Korean mistletoe.
There is accumulating evidence that both types of MLs are able to induce an anti-angiogenic response in the
host suggesting that the anti-metastatic effect observed
on a series of tumour cell lines in mice is in part due to
an inhibition of tumour-induced angiogenesis and in part
due to an induction of apoptosis
Dietary mistletoe lectin supplementation and reduced growth of a murine non-Hodgkin lymphoma
The growth of a murine non-Hodgkin
lymphoma (NHL) tumour has been shown to be reduced
by incorporating mistletoe lectin (ML-1) into the diet.
The morphological characteristics of NHL tumours in
mice fed ML-1-supplemented diets were different from
those in LA (control)-fed mice. The degree of mitotic
activity was lower and nuclear area reduced. The degree
of lymphocyte infiltration was increased in tumours
from ML-1 fed mice and this was accompanied by a
high incidence of apoptotic bodies. Visual observation of
NHL tumours from individuals fed ML-1 diet showed a
poorly developed blood supply in contrast to control-fed
mice. A major reduction in number of blood capillaries
in NHL tumours was confirmed by microscopic
evaluation of tumour sections. The results suggested an
anti-angiogenic response in ML-1-fed mice. The feeding
of ML-1 compared to control diet thus provided several
identifiable changes in the morphology of NHL tumours
which were consistent with the observed reduction in
tumour weight. There was no longer histological
evidence of viable tumour in 25% mice fed the ML-1
diet for 11 days. Morphological studies of the small
bowel indicated (a) that the lectin induces hyperplasia,
and (b) that the lectin binds avidly to lymphoid tissue of
P e y e r’s patches. There was evidence of limited
endocytosis of the lectin. An experiment where ML-3
was added to the diet of mice three days after inoculation
of tumour cells showed that the lectin was able to slow
down further growth of an established tumour. The
results show that ML lectins induce powerful anti-cancer
effects when provided by the oral route
The induction of gut hyperplasia by phytohaemagglutinin in the diet and limitation of tumour growth
The growth of a transplantable murine non-
Hodgkin lymphoma tumour, developing either intraperitoneally
as an ascites tumour or subcutaneously as a
solid tumour, has been shown to be markedly diminished
by including phytohaemagglutinin (PHA), a lectin
present in raw kidney bean (I'haseolus vulgaris) in the
diet. In NMRl mice fed PHA within the range 0.45-7.0
mg/g diet, tumours which developed during a 10 day
period after subcutaneous injection of cells were about
35% of the dry weight of those in lactalbumin-fed
(control) animals. The reduced rate of growth occurred
in a dose-dependent manner within the range 0.45-3.5
mg/g diet. Based on these observations it has been
suggested that a competition between the gut epithelium
undergoing hyperplasia and the developing tumour may
occur for nutrients from a common body pool, and this
may be an important factor with regard to the observed
initial low level of tumour growth following the feeding
of a PHA-containing diet. Observations which showed
that the level of hyperplasia of the small bowel in
response to feeding the PHA diets was higher in noninjected
mice compared to those which had been injected
with tumour cells substantiated the concept of
competition between gut and tumour for nutrients etc.
required for growth. Experiments with a second murine
tumour cell line (a plasmacytoma) in Balblc mice gave
similar results indicating that the effect of PHA was not
restricted to a single tumour system
Probing for Membrane Domains in the Endoplasmic Reticulum: Retention and Degradation of Unassembled MHC Class I Molecules
Quality control of protein biosynthesis requires ER-retention and ER-associated degradation (ERAD) of unassembled/misfolded molecules. Although some evidence exists for the organization of the ER into functionally distinct membrane domains, it is unknown if such domains are involved in the retention and ERAD of unassembled proteins. Here, it is shown that unassembled MHC class I molecules are retained in the ER without accumulating at ER-exit sites or in the ERGIC of β2m(−/−) cells. Furthermore, these molecules did not cluster in the ER membrane and appeared to be highly mobile even when ERAD or their association with calnexin were inhibited. However, upon ATP depletion, they were reversibly segregated into an ER membrane domain, distinct from ER exit sites, which included calnexin and COPII, but not the ERGIC marker protein p58. This quality control domain was also observed upon prolonged inhibition of proteasomes. Microtubules were required for its appearance. Segregation of unfolded proteins, ER-resident chaperones, and COPII may be a temporal adaptation to cell stress