cell proliferation and sensitize cells to apoptosis induction. Silymarin is reported
to induce apoptosis in malignant melanoma cells by increasing the expression of
Fas-associated proteins with death domain (FADD) followed by cleavage of
procaspase-8 that induces apoptosis, cleavage of poly(ADP-ribose) polymerase
(PARP), caspase-9, and caspase-3, and decreasing survivin levels in human prostate
cancer. Silymarin also inhibited Akt activity, which was associated with activation
of caspase-9 and caspase-3 as well as PARP cleavage, in leukemic cells [86]. It has
been shown that dietary supplementation with silymarin inhibits 3,20-dimethyl-4aminobiphenyl-induced prostate carcinogenesis in male F344 rats by increasing
apoptosis and modification of cell proliferation [87].
Many isolated steroidal saponins have been shown to be either cytostatic or
cytotoxic to HL-60 human leukemia cell lines [43]. Lee et al. reported the in vitro
tumor activity of saponins in different cancer cell line and suggested that it could be
a good candidate for treatment of pulmonary cancer cells [88].
EGCG inhibits cancer-associated stages and exerts an inhibitory effect on
DNA methylation via blocking the performance of DNA methyltransferases,
strong free-radical scavenging, and antioxidant activities. Recently, EGCG has
been shown to inhibit lipopolysaccharide-induced NO production and iNOS gene
expression in isolated peritoneal macrophages by decreasing the activation of
NF-kB [89]. EGCG inhibited platelet-derived growth factor (PDGF)-induced
apoptosis and cell cycle-regulating pathways of vascular smooth muscle cells,
resulting in inhibition of tumor growth, metastasis, and angiogenesis in vivo [77].
In a study that tested the effect of EGCG on oral cancer cell lines along with
curcumin, EGCG blocked cell division in G1, whereas curcumin blocked cell
division in S/G2M. EGCG has antiproliferative activities on tumor cells through
the blockage of growth factor binding to the receptor and the suppression of
mitogenic signal transduction [89]. Apoptosis induction by EGCG is more
prominent in many cancer cells without affecting normal cells because NF-kB
is activated in cancer cells. EGCG-induced apoptosis in tumor cells may be
mediated through direct inhibition of cyclin-dependent kinases and NF-kB inactivation [24]. EGCG also induces the expression of p21 and p27 while decreasing the expression of cyclin D1 and the phosphorylation of retinoblastoma.
However, EGCG inhibited lipopolysaccharide-induced phosphorylation of IkB
kinase complex (IKK), but failed to affect NF-kB luciferase reporter gene
activation in human colon cancer (HT-29) cells, suggesting that EGCG modulation of NF-kB transcriptional activity is not necessarily dependent on IkBa
degradation and subsequent release of NF-kB proteins. EGCG downregulates
NF-kB, inducing kinase expression in human lung cancer (PC-9) cells. Activation of NF-kB promotes transcriptional upregulation of Bcl-2 and Bcl-XL.
Negative regulation of NF-kB by EGCG decreases expression of the
proapoptotic protein Bcl-2 [90]. In human prostate carcinoma LNCaP cells,
treatment with EGCG induced apoptosis and was associated with stabilization
of p53 and also with a downregulation of NF-kB activity, resulting in a
decreased expression of the anti-apoptotic protein Bcl-2 [89]. EGCG (70% lethal
dose) at the supra-pharmacological concentration of 10 mg/mL increased the
212
S. Maya et al.
to induce apoptosis in malignant melanoma cells by increasing the expression of
Fas-associated proteins with death domain (FADD) followed by cleavage of
procaspase-8 that induces apoptosis, cleavage of poly(ADP-ribose) polymerase
(PARP), caspase-9, and caspase-3, and decreasing survivin levels in human prostate
cancer. Silymarin also inhibited Akt activity, which was associated with activation
of caspase-9 and caspase-3 as well as PARP cleavage, in leukemic cells [86]. It has
been shown that dietary supplementation with silymarin inhibits 3,20-dimethyl-4aminobiphenyl-induced prostate carcinogenesis in male F344 rats by increasing
apoptosis and modification of cell proliferation [87].
Many isolated steroidal saponins have been shown to be either cytostatic or
cytotoxic to HL-60 human leukemia cell lines [43]. Lee et al. reported the in vitro
tumor activity of saponins in different cancer cell line and suggested that it could be
a good candidate for treatment of pulmonary cancer cells [88].
EGCG inhibits cancer-associated stages and exerts an inhibitory effect on
DNA methylation via blocking the performance of DNA methyltransferases,
strong free-radical scavenging, and antioxidant activities. Recently, EGCG has
been shown to inhibit lipopolysaccharide-induced NO production and iNOS gene
expression in isolated peritoneal macrophages by decreasing the activation of
NF-kB [89]. EGCG inhibited platelet-derived growth factor (PDGF)-induced
apoptosis and cell cycle-regulating pathways of vascular smooth muscle cells,
resulting in inhibition of tumor growth, metastasis, and angiogenesis in vivo [77].
In a study that tested the effect of EGCG on oral cancer cell lines along with
curcumin, EGCG blocked cell division in G1, whereas curcumin blocked cell
division in S/G2M. EGCG has antiproliferative activities on tumor cells through
the blockage of growth factor binding to the receptor and the suppression of
mitogenic signal transduction [89]. Apoptosis induction by EGCG is more
prominent in many cancer cells without affecting normal cells because NF-kB
is activated in cancer cells. EGCG-induced apoptosis in tumor cells may be
mediated through direct inhibition of cyclin-dependent kinases and NF-kB inactivation [24]. EGCG also induces the expression of p21 and p27 while decreasing the expression of cyclin D1 and the phosphorylation of retinoblastoma.
However, EGCG inhibited lipopolysaccharide-induced phosphorylation of IkB
kinase complex (IKK), but failed to affect NF-kB luciferase reporter gene
activation in human colon cancer (HT-29) cells, suggesting that EGCG modulation of NF-kB transcriptional activity is not necessarily dependent on IkBa
degradation and subsequent release of NF-kB proteins. EGCG downregulates
NF-kB, inducing kinase expression in human lung cancer (PC-9) cells. Activation of NF-kB promotes transcriptional upregulation of Bcl-2 and Bcl-XL.
Negative regulation of NF-kB by EGCG decreases expression of the
proapoptotic protein Bcl-2 [90]. In human prostate carcinoma LNCaP cells,
treatment with EGCG induced apoptosis and was associated with stabilization
of p53 and also with a downregulation of NF-kB activity, resulting in a
decreased expression of the anti-apoptotic protein Bcl-2 [89]. EGCG (70% lethal
dose) at the supra-pharmacological concentration of 10 mg/mL increased the
212
S. Maya et al.