phosphorylation also enhanced the anti-angiogenic effects of EGCG through transcriptional activation of FOXO [77, 89].
2.5 Antimetastatic Effect
Cancer metastasis, which depends on the motility and invasiveness of cancer cells,
can complicate clinical management and is a primary cause of cancer deaths.
A study of curcumin in metastatic melanoma demonstrated a dose-dependent
reduction in binding to extracellular matrix proteins, decreased expression of
a5b1 and a(V)b3 integrin receptors, and increased expression of various
antimetastatic proteins including tissue inhibitor metalloproteinase 2 (TIMP-2),
nonmetastatic gene 23, and E-cadherin [13]. E-cadherin expression is important
in maintaining the integrity of intercellular adhesion though binding to various
catenins (including b-catenin), and loss of E-cadherin is associated with an
increased tendency for tumor metastasis. Antimetastatic effects of curcumin have
also been demonstrated in the MDA-MB-231 breast cancer cell line, resulting in
decreased expression of MMPs, ICAM-1, and chemokine receptor 4, and
suppressed cell migration and invasion [97, 98]. Silibinin has the potential to reduce
MMP-2 and urokinase-type plasminogen activator (u-PA) expression through
reducing ERK1/2 and Akt phosphorylation, which in turn leads to reduced invasiveness of cancer cells [99]. EGCG blocks urokinase, an enzyme that is essential
for cancer growth and metastasis formation, by interfering with the enzyme’s
ability to recognize its substrates [100].
3 Significance of Polymeric Nanocarriers
Conventional natural products have inherent problems of stability, solubility,
toxicity, and bioavailability. Chemopreventive treatments require the administration of low doses of chemopreventive agents to avoid toxic side effects and, hence,
the bioavailability of these agents becomes a crucial factor [101]. The chemical
structure of the phytochemicals determines their gut absorption, and the urine and
plasma levels represent good markers for establishing the bioavailability of
polyphenols and their metabolites. Generally, less than 10% of polyphenols, or
their metabolites, ingested are found in urine and plasma [102]. Another issue is the
loss of activity after metabolism because the metabolites may not be biologically
active. Only a small proportion of the molecules remain available following oral
administration due to insufficient gastric residence time, low permeability, solubility
within the gut, and conditions in the gastrointestinal tract (pH, enzymes, presence
of other nutrients), all of which limit the activity and potential health benefits of
these nutraceutical components [103]. The major factors that limit the therapeutic
214
S. Maya et al.
2.5 Antimetastatic Effect
Cancer metastasis, which depends on the motility and invasiveness of cancer cells,
can complicate clinical management and is a primary cause of cancer deaths.
A study of curcumin in metastatic melanoma demonstrated a dose-dependent
reduction in binding to extracellular matrix proteins, decreased expression of
a5b1 and a(V)b3 integrin receptors, and increased expression of various
antimetastatic proteins including tissue inhibitor metalloproteinase 2 (TIMP-2),
nonmetastatic gene 23, and E-cadherin [13]. E-cadherin expression is important
in maintaining the integrity of intercellular adhesion though binding to various
catenins (including b-catenin), and loss of E-cadherin is associated with an
increased tendency for tumor metastasis. Antimetastatic effects of curcumin have
also been demonstrated in the MDA-MB-231 breast cancer cell line, resulting in
decreased expression of MMPs, ICAM-1, and chemokine receptor 4, and
suppressed cell migration and invasion [97, 98]. Silibinin has the potential to reduce
MMP-2 and urokinase-type plasminogen activator (u-PA) expression through
reducing ERK1/2 and Akt phosphorylation, which in turn leads to reduced invasiveness of cancer cells [99]. EGCG blocks urokinase, an enzyme that is essential
for cancer growth and metastasis formation, by interfering with the enzyme’s
ability to recognize its substrates [100].
3 Significance of Polymeric Nanocarriers
Conventional natural products have inherent problems of stability, solubility,
toxicity, and bioavailability. Chemopreventive treatments require the administration of low doses of chemopreventive agents to avoid toxic side effects and, hence,
the bioavailability of these agents becomes a crucial factor [101]. The chemical
structure of the phytochemicals determines their gut absorption, and the urine and
plasma levels represent good markers for establishing the bioavailability of
polyphenols and their metabolites. Generally, less than 10% of polyphenols, or
their metabolites, ingested are found in urine and plasma [102]. Another issue is the
loss of activity after metabolism because the metabolites may not be biologically
active. Only a small proportion of the molecules remain available following oral
administration due to insufficient gastric residence time, low permeability, solubility
within the gut, and conditions in the gastrointestinal tract (pH, enzymes, presence
of other nutrients), all of which limit the activity and potential health benefits of
these nutraceutical components [103]. The major factors that limit the therapeutic
214
S. Maya et al.