135 research outputs found
Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action
Introduction The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA).
Methods KPL-1 cell growth was assessed by colorimetric 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21Cip1/Waf1, cyclin D1, Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet.
Results CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G0/G1 arrest, which involved increased expression of p53 and p21Cip1/Waf1, and decreased expression of cyclin D1. CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner.
Conclusion CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system.</p
Experimental models for carcinogenesis in the house musk shrew, Suncus murinus, lnsectivora
Animal carcinogenicity studies have niainly
been performed on rodents. From the phylogenetic point
of view, animals closer to humans must be included in
these studies. lnsectivora are considered to be the most
prirnitive placental mammals and much closer to the
early primates than rodents. Among the insectivora, the
house musk shrew (Suncus mul-inus, family Soracidae),
has been bred under laboratory condition. This animal is
small having a short life span, and a comparatively low
incidence of spontaneous tumor provides a useful animal
model for tumor induction studies. We have examined
the carcinogenicity of severa1 chemicals known to
produce tumors in rodents and found shrews: in general,
to be sensitive to these chemicals but often showed
different targets compared to rodents, and some
chemicals tested were demonstrated not to be
carcinogenic. Here we describe the carcinogenic studies
performed in our laboratory and review other works
including the occurrence of spontaneous tumors in
shrews. Shrew carcinogenesis may fill up the gap of
knowledge existing between the rodents and hurnan
beings
Animal models for retinitis pigmentosa induced by MNU; disease progression, mechanisms and therapeutic trials
Retinitis pigmentosa (RP) is a group of
inherited neurodegenerative diseases in humans
characterized by loss of photoreceptor cells leading to
visual disturbance and eventually to blindness. A single
systemic administration of N-methyl-N-nitrosourea
(MNU) causes retinal degeneration in various animal
species. The retinal degeneration is highly reproducible,
and the photoreceptor cell loss occurs within seven days
after MNU administration via apoptosis resembling
human RP. Here, we describe the disease progression,
disease mechanisms, and therapeutic trials of MNUinduced
retinal degeneration
Role of fatty acids in malignancy and visual impairment, Epidemiological evidence and experimental studies
International variation in breast and colon
cancer incidence is positively related to total fat intake.
However, total fat consists of different fatty acid
families, e.g., saturated fatty acids (SFAs),
monounsaturated fatty acids (MUFAs), and n-3 and n-6
polyunsaturated fatty acids (PUFAs). Epidemiological
evidence and experimental studies suggest that these
fatty acid families have different effects on breast and
colon carcinogenesis. Therefore the action of each fatty
acid on carcinogenesis should be evaluated separately.
Although it is difficult to establish firm conclusions on
the effect of each fatty acid in human epidemiological
studies, experimental studies on animals and cultured
cells suggest that n-6 PUFAs (linoleic acid and
arachidonic acid) may have a tumor promoting effect,
while n-3 PUFAs (eicosapentaenoic acid,
docosahexaenoic acid and a-linolenic acid) and
conjugated fatty acids (CFAs; a mixture of positional
and geometric isomers of PUFAs with conjugated double
bonds) exert an inhibitory effect on tumor growth. SFAs
such as palmitic acid and stearic acid show little or no
tumor promoting effect, and the action of oleic acid, a MUFA, is inconclusive. In addition to regulation of
abnormal cell growth seen in cancers, fatty acids also
control cell loss seen in degenerative eye diseases, such
as degeneration of lens material in cataract and
degeneration of photoreceptor cells in retinitis
pigmentosa. Experiments suggest that n-6 PUFAs cause
deleterious effects, while n-3 PUFAs result in beneficial
effects on the lens and retina. In particular,
docosahexaenoic acid is known to be effective in
rescuing photoreceptor cells from damage. Thus,
understanding the function of each fatty acid is likely to be important for making progress in treating these and
other diseases
- …