Taka
2009-04-15 15:19:18 UTC
Experimental Biology and Medicine 230:217-223 (2005)
Anticancer Effects of a Plant Lignan 7-Hydroxymatairesinol on a
Prostate Cancer Model In Vivo
Clinical intervention studies and experimental studies with lignan-
rich diets suggest that lignans may have inhibitory effects on
prostate cancer, but no clinical or experimental studies with purified
lignans have been published. The purpose of this study was to
investigate the effect of a plant lignan 7-hydroxymatairesinol (HMR)
on LNCaP human prostate cancer xenografts in athymic mice. Athymic
nude male mice were injected subcutaneously with LNCaP cells. Starting
3 days after tumor cell injections, a control diet or a control diet
supplemented with 0.15% or 0.30% of HMR was administered to mice and
the tumor take rate and growth was observed for 9 weeks. HMR diet
inhibited the growth of LNCaP tumors. Mice treated with HMR had
smaller tumor volume, lower tumor take rate, increased proportion of
nongrowing tumors, and higher tumor cell apoptotic index compared with
controls. Furthermore, the cell proliferation index was reduced in
mice receiving the 0.30% HMR diet compared with mice receiving the
control diet. Our results suggest that dietary HMR started at the
early phase of the tumor development inhibits the growth of the LNCaP
human prostate cancer xenografts in athymic male mice.
The hypothesis that a lignan-rich diet inhibits the development and
growth of hormone-sensitive prostate cancer is supported by the data
from several experimental studies. A diet high in rye bran (30%)
increased apoptosis in Dunning R3327 PAP prostate tumor implants in
rats (1, 2), and in the human androgen-sensitive LNCaP xenografts in
BALB/c athymic mice (3) when compared with animals receiving a
semipurified control diet. Furthermore, in a transgenic adenocarcinoma
mouse prostate (TRAMP) model, dietary flaxseed (5%) inhibited the
growth and progression of the cancers (4).
To determine if lignans per se are biologically active, purified
compounds have to be investigated. We chose to use a plant lignan 7-
hydroxymatairesinol (HMR) because it is structurally closely related
to matairesinol (MR; Fig. 1). MR is one of the plant lignans found in
many foods but only in small quantities (5, 6), and rich dietary
sources suitable for MR isolation are not available. HMR, in contrast,
is found in very high quantities in knots of Norway spruce (Picea
abies) (7), and can be extracted in large amounts sufficient for a
long-term in vivo experiment. Similar to abundant dietary plant
lignans secoisolariciresinol diglycoside (SDG) and MR, HMR is also
metabolized into mammalian lignan enterolactone (ENL) in vivo (8–13).
Because of the limited availability of most lignans in large amounts,
only a small number of studies have been conducted using purified
compounds. Plant lignans, such as SDG, sesamin, and HMR have been
tested in experimental models for hormone-dependent cancers. SDG
isolated from flaxseed and HMR have both been shown to inhibit the
growth of mammary carcinoma and intestinal tumors in rodent models
(11, 12, 14–16), whereas sesame seed lignan sesamin added to
semipurified diet has been demonstrated to decrease the multiplicity
of the mammary tumors (17).
In this study, we examined the effect of dietary HMR on growth of
LNCaP xenografts in athymic nude mice. LNCaP is an androgen-sensitive
human prostate adenocarcinoma cell line (18, 19). To our knowledge,
this is the first study done with a purified lignan in an experimental
prostate cancer model in vivo.
MORE AT: http://www.ebmonline.org/cgi/content/full/230/3/217
Prostate. 2000 Mar 1;42(4):304-14.
Rye bran and soy protein delay growth and increase apoptosis of human
LNCaP prostate adenocarcinoma in nude mice.
Bylund A, Zhang JX, Bergh A, Damber JE, Widmark A, Johansson A,
Adlercreutz H, Aman P, Shepherd MJ, Hallmans G.
Department of Oncology, University of Umeå, Umeå, Sweden.
BACKGROUND: In this study, we investigated whether dietary
intervention could inhibit tumor growth of an androgen-sensitive human
prostatic cancer. METHODS: LNCaP cells were transplanted
subcutaneously in nude-mice. The animals were then put on different
diets and tumor take, tumor growth and prostate specific antigen (PSA)
secretion were studied during 9 weeks. RESULTS: Palpable tumors
developed in 75% of the tumor-cell injected sites in animals fed a
control diet (corn starch, sucrose, etc.) whereas, for animals given
rye bran (RB), ethyl acetate extraction from rye bran supplemented
cellulose based diets (CCEE), palpable tumors were seen in only 30%
and for soy protein based diets (SCC) 50% of the transplantation
sites, respectively. The tumors that grew to palpable size in the rye
(RB) and soy (SCC) groups were smaller and secreted less PSA than
those in the control group. In the rye and soy groups tumor cell
apoptosis was increased, but cell proliferation was unaffected.
Addition of fat to the rye diet reduced its effect on prostate cancer
growth. CONCLUSIONS: Factors in rye bran and soy protein may inhibit
prostate cancer growth. The effect is more apparent for rye than for
soy. Further studies are needed to identify the effective substances
and to explore the mechanism of action. Copyright 2000 Wiley-Liss,
Inc.
PMID: 10679760
------------------------------------
One has to ask the question what else would rye lignans kill in the
body before using them for PC prevention.
Taka
Anticancer Effects of a Plant Lignan 7-Hydroxymatairesinol on a
Prostate Cancer Model In Vivo
Clinical intervention studies and experimental studies with lignan-
rich diets suggest that lignans may have inhibitory effects on
prostate cancer, but no clinical or experimental studies with purified
lignans have been published. The purpose of this study was to
investigate the effect of a plant lignan 7-hydroxymatairesinol (HMR)
on LNCaP human prostate cancer xenografts in athymic mice. Athymic
nude male mice were injected subcutaneously with LNCaP cells. Starting
3 days after tumor cell injections, a control diet or a control diet
supplemented with 0.15% or 0.30% of HMR was administered to mice and
the tumor take rate and growth was observed for 9 weeks. HMR diet
inhibited the growth of LNCaP tumors. Mice treated with HMR had
smaller tumor volume, lower tumor take rate, increased proportion of
nongrowing tumors, and higher tumor cell apoptotic index compared with
controls. Furthermore, the cell proliferation index was reduced in
mice receiving the 0.30% HMR diet compared with mice receiving the
control diet. Our results suggest that dietary HMR started at the
early phase of the tumor development inhibits the growth of the LNCaP
human prostate cancer xenografts in athymic male mice.
The hypothesis that a lignan-rich diet inhibits the development and
growth of hormone-sensitive prostate cancer is supported by the data
from several experimental studies. A diet high in rye bran (30%)
increased apoptosis in Dunning R3327 PAP prostate tumor implants in
rats (1, 2), and in the human androgen-sensitive LNCaP xenografts in
BALB/c athymic mice (3) when compared with animals receiving a
semipurified control diet. Furthermore, in a transgenic adenocarcinoma
mouse prostate (TRAMP) model, dietary flaxseed (5%) inhibited the
growth and progression of the cancers (4).
To determine if lignans per se are biologically active, purified
compounds have to be investigated. We chose to use a plant lignan 7-
hydroxymatairesinol (HMR) because it is structurally closely related
to matairesinol (MR; Fig. 1). MR is one of the plant lignans found in
many foods but only in small quantities (5, 6), and rich dietary
sources suitable for MR isolation are not available. HMR, in contrast,
is found in very high quantities in knots of Norway spruce (Picea
abies) (7), and can be extracted in large amounts sufficient for a
long-term in vivo experiment. Similar to abundant dietary plant
lignans secoisolariciresinol diglycoside (SDG) and MR, HMR is also
metabolized into mammalian lignan enterolactone (ENL) in vivo (8–13).
Because of the limited availability of most lignans in large amounts,
only a small number of studies have been conducted using purified
compounds. Plant lignans, such as SDG, sesamin, and HMR have been
tested in experimental models for hormone-dependent cancers. SDG
isolated from flaxseed and HMR have both been shown to inhibit the
growth of mammary carcinoma and intestinal tumors in rodent models
(11, 12, 14–16), whereas sesame seed lignan sesamin added to
semipurified diet has been demonstrated to decrease the multiplicity
of the mammary tumors (17).
In this study, we examined the effect of dietary HMR on growth of
LNCaP xenografts in athymic nude mice. LNCaP is an androgen-sensitive
human prostate adenocarcinoma cell line (18, 19). To our knowledge,
this is the first study done with a purified lignan in an experimental
prostate cancer model in vivo.
MORE AT: http://www.ebmonline.org/cgi/content/full/230/3/217
Prostate. 2000 Mar 1;42(4):304-14.
Rye bran and soy protein delay growth and increase apoptosis of human
LNCaP prostate adenocarcinoma in nude mice.
Bylund A, Zhang JX, Bergh A, Damber JE, Widmark A, Johansson A,
Adlercreutz H, Aman P, Shepherd MJ, Hallmans G.
Department of Oncology, University of Umeå, Umeå, Sweden.
BACKGROUND: In this study, we investigated whether dietary
intervention could inhibit tumor growth of an androgen-sensitive human
prostatic cancer. METHODS: LNCaP cells were transplanted
subcutaneously in nude-mice. The animals were then put on different
diets and tumor take, tumor growth and prostate specific antigen (PSA)
secretion were studied during 9 weeks. RESULTS: Palpable tumors
developed in 75% of the tumor-cell injected sites in animals fed a
control diet (corn starch, sucrose, etc.) whereas, for animals given
rye bran (RB), ethyl acetate extraction from rye bran supplemented
cellulose based diets (CCEE), palpable tumors were seen in only 30%
and for soy protein based diets (SCC) 50% of the transplantation
sites, respectively. The tumors that grew to palpable size in the rye
(RB) and soy (SCC) groups were smaller and secreted less PSA than
those in the control group. In the rye and soy groups tumor cell
apoptosis was increased, but cell proliferation was unaffected.
Addition of fat to the rye diet reduced its effect on prostate cancer
growth. CONCLUSIONS: Factors in rye bran and soy protein may inhibit
prostate cancer growth. The effect is more apparent for rye than for
soy. Further studies are needed to identify the effective substances
and to explore the mechanism of action. Copyright 2000 Wiley-Liss,
Inc.
PMID: 10679760
------------------------------------
One has to ask the question what else would rye lignans kill in the
body before using them for PC prevention.
Taka