Cell Wall Polysaccharides of Marine Algae 22.5 Biological Activities and Medicinal Applications 563
Part D | 22.5
ulating innate immunity as well as adaptive immune
responses by producing an array of cytokines such
as interleukins (IL) IL-1ˇ and IL-6, tumor necrosis
factor (TNF)-˛ and interferon- (INF- ), and various types of chemokines such as RANTES (regulated
on activation, normal T-cell expressed and secreted),
monocyte chemotactic protein (MCP)-1, macrophage
inflammatory protein (MIP)-1˛, thymus and activation regulated chemokine (TARC), etc. [22.308, 309].
Polysaccharide macromolecules may interact with specific membrane receptors of macrophages including
Toll-like receptor (TLR)-4, cluster of differentiation
(CD)-14, complement receptor (CR)-3 and scavenger
receptors (SR). As a result, the intracellular signaling
pathways are promoted, involving mitogen-activated
protein kinases (MAPK) and transcription factors. Activation of macrophages via MAPK induces the production of both nitric oxide (NO) and cytokines. Partially,
interleukin-12 (IL-12) stimulates the development of Tcells, which produce interleukin-2 (IL-2) that, in turn,
activates proliferation of natural killer (NK) cells, representing a first line of defence organism against both
primary tumors and metastases. NK cells produce other
cytokines, including interferon (INF)- , which can further provoke macrophages in their stimulation of T-cells
via induction of IL-12. NK-mediated killing of target
cells by apoptosis is facilitated by activation of caspase cascades [22.310]. Many algal polysaccharides
have been reported for their immunomodulatory activities as they stimulate the activity of macrophages.
Polysaccharides from the red algae Porphyra yezoensis [22.311, 312] and Gracilaria verrucosa [22.313]
are reported to have macrophage-stimulating activity
in vitro and in vivo. A fucoidan isolated from the
sporophyll of brown alga Undaria pinnatifida (Korean
Miyeokgui, Japanese Mekabu) stimulated macrophages
to produce cytokines (IL-6, TNF-˛) and chemokines
(RANTES, MIP-1˛) from macrophages and splenocytes [22.125]. Carrageenan isolated from red algae
promotes mice leukocytes to produce TNF-˛ [22.314].
A sulfated water-soluble polysaccharide isolated from
the green alga Capsosiphon fulvescens is reported to
stimulate macrophage to release TNF-˛ and IL-6, and
induce the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These
enzymes are responsible for the production of NO and
prostaglandin E2 (PGE2), respectively [22.315]. A sulfated glucuronorhamnan, an ulvan, of the green algae
Ulva rigida, is also reported to stimulate macrophage
to secrete PGE 2 and induce an increase in COX-2 and
NOS-2 expression [22.316]. Immunomodulation and
other biological activities of marine algal polysaccharides are reviewed in Table 22.12.
22.5.2 Antitumor
and Antimutagenic Activities
The antitumor effect of fucoidans and other sulfated algal polysaccharides that are nontoxic for tumor cells
is commonly associated with the following indirect
activities:
1. The inhibition of tumor cell proliferation
2. The stimulation of the apoptosis of tumor cells
3. Blocking tumor cell metastasis
4. The inhibition of blood vessel formation
5. The enhancement of various immune responses
[22.393].
Partially, antitumor and antimetastatic activity of
these polysaccharides is mediated by increased NO production by stimulated macrophages [22.364], activation
of NK cells via specific cytokines, and/or induction
of caspase-dependent cancer cell apoptosis via inhibition of specific MAPK [22.310, 381, 394]. Fucoidan
may also activate caspase-independent apoptosis via
activation of ROS-mediated MAPK and regulation of
the Bcl-2 family protein-mediated mitochondrial pathway [22.395]. Fucoidan from Cladosiphon okamuranus
significantly inhibited in vivo and in vitro growth and
induced apoptosis of human T-cell leukaemia virus
type 1 (HTLV-1) infected T-cells. This fucoidan also
inhibited in vivo growth of model HTLV-1-induced
tumors based on subcutaneously transplanted infected
T-cell lines in immune deficient mice [22.396]. Both
Miyeokgui (Undaria pinnatifida sporophyll) and commercial (Fucus vesiculosus) fucoidans showed antitumor activity against four types of cancer, i. e., PC-3
(prostate cancer), HeLa (cervical cancer), A549 (alveolar carcinoma), and HepG2 (hepatocellular carcinoma)
cells [22.137]. Fucoidans blocked tumor cell adhesion that could be important for antimetastatic effects
[22.397, 398]. Fucoidan from Fucus evanescens produced an inhibitory effect against metastasis and potentiated antimetastatic, but not antitumor, effects of
cyclophosphamide [22.348]. Fucoidans suppress angiogenesis and thus reduce the supply of tumor tissues [22.399, 400]. Fucoidans stimulate proliferation
of macrophages [22.401] and mediate tumor destruction through Th1 cell and NK cell responses [22.380].
Fucoidans activate lymphocytes and macrophages mediated by the production of NO, H 2 O 2 , and cy-
Part D | 22.5
ulating innate immunity as well as adaptive immune
responses by producing an array of cytokines such
as interleukins (IL) IL-1ˇ and IL-6, tumor necrosis
factor (TNF)-˛ and interferon- (INF- ), and various types of chemokines such as RANTES (regulated
on activation, normal T-cell expressed and secreted),
monocyte chemotactic protein (MCP)-1, macrophage
inflammatory protein (MIP)-1˛, thymus and activation regulated chemokine (TARC), etc. [22.308, 309].
Polysaccharide macromolecules may interact with specific membrane receptors of macrophages including
Toll-like receptor (TLR)-4, cluster of differentiation
(CD)-14, complement receptor (CR)-3 and scavenger
receptors (SR). As a result, the intracellular signaling
pathways are promoted, involving mitogen-activated
protein kinases (MAPK) and transcription factors. Activation of macrophages via MAPK induces the production of both nitric oxide (NO) and cytokines. Partially,
interleukin-12 (IL-12) stimulates the development of Tcells, which produce interleukin-2 (IL-2) that, in turn,
activates proliferation of natural killer (NK) cells, representing a first line of defence organism against both
primary tumors and metastases. NK cells produce other
cytokines, including interferon (INF)- , which can further provoke macrophages in their stimulation of T-cells
via induction of IL-12. NK-mediated killing of target
cells by apoptosis is facilitated by activation of caspase cascades [22.310]. Many algal polysaccharides
have been reported for their immunomodulatory activities as they stimulate the activity of macrophages.
Polysaccharides from the red algae Porphyra yezoensis [22.311, 312] and Gracilaria verrucosa [22.313]
are reported to have macrophage-stimulating activity
in vitro and in vivo. A fucoidan isolated from the
sporophyll of brown alga Undaria pinnatifida (Korean
Miyeokgui, Japanese Mekabu) stimulated macrophages
to produce cytokines (IL-6, TNF-˛) and chemokines
(RANTES, MIP-1˛) from macrophages and splenocytes [22.125]. Carrageenan isolated from red algae
promotes mice leukocytes to produce TNF-˛ [22.314].
A sulfated water-soluble polysaccharide isolated from
the green alga Capsosiphon fulvescens is reported to
stimulate macrophage to release TNF-˛ and IL-6, and
induce the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These
enzymes are responsible for the production of NO and
prostaglandin E2 (PGE2), respectively [22.315]. A sulfated glucuronorhamnan, an ulvan, of the green algae
Ulva rigida, is also reported to stimulate macrophage
to secrete PGE 2 and induce an increase in COX-2 and
NOS-2 expression [22.316]. Immunomodulation and
other biological activities of marine algal polysaccharides are reviewed in Table 22.12.
22.5.2 Antitumor
and Antimutagenic Activities
The antitumor effect of fucoidans and other sulfated algal polysaccharides that are nontoxic for tumor cells
is commonly associated with the following indirect
activities:
1. The inhibition of tumor cell proliferation
2. The stimulation of the apoptosis of tumor cells
3. Blocking tumor cell metastasis
4. The inhibition of blood vessel formation
5. The enhancement of various immune responses
[22.393].
Partially, antitumor and antimetastatic activity of
these polysaccharides is mediated by increased NO production by stimulated macrophages [22.364], activation
of NK cells via specific cytokines, and/or induction
of caspase-dependent cancer cell apoptosis via inhibition of specific MAPK [22.310, 381, 394]. Fucoidan
may also activate caspase-independent apoptosis via
activation of ROS-mediated MAPK and regulation of
the Bcl-2 family protein-mediated mitochondrial pathway [22.395]. Fucoidan from Cladosiphon okamuranus
significantly inhibited in vivo and in vitro growth and
induced apoptosis of human T-cell leukaemia virus
type 1 (HTLV-1) infected T-cells. This fucoidan also
inhibited in vivo growth of model HTLV-1-induced
tumors based on subcutaneously transplanted infected
T-cell lines in immune deficient mice [22.396]. Both
Miyeokgui (Undaria pinnatifida sporophyll) and commercial (Fucus vesiculosus) fucoidans showed antitumor activity against four types of cancer, i. e., PC-3
(prostate cancer), HeLa (cervical cancer), A549 (alveolar carcinoma), and HepG2 (hepatocellular carcinoma)
cells [22.137]. Fucoidans blocked tumor cell adhesion that could be important for antimetastatic effects
[22.397, 398]. Fucoidan from Fucus evanescens produced an inhibitory effect against metastasis and potentiated antimetastatic, but not antitumor, effects of
cyclophosphamide [22.348]. Fucoidans suppress angiogenesis and thus reduce the supply of tumor tissues [22.399, 400]. Fucoidans stimulate proliferation
of macrophages [22.401] and mediate tumor destruction through Th1 cell and NK cell responses [22.380].
Fucoidans activate lymphocytes and macrophages mediated by the production of NO, H 2 O 2 , and cy-