IL-2, IL-6, IL-8, and IL-12). This secretion is inhibited by curcumin. The
arachadonic acid pathway for eicosanoid biosynthesis is an important participant
in the inflammatory response, generating a host of reactive lipid products including
leukotrienes, prostaglandins, prostacyclins, and thromboxanes. Curcumin has been
shown to decrease the metabolism of arachadonic acid by downregulating the
activity of LOX and COX-2, both at the transcriptional level as well as via posttranslational enzyme inhibition. Curcumin inhibited prostaglandin E2 biosynthesis
through direct inhibition of the microsomal prostaglandin E2 synthase-1 enzyme.
Studies have demonstrated that silymarin is a potent inhibitor of NF-kB activation in response to TNF-a. This effect was mediated through the inhibition of
phosphorylation and degradation of IkB [73]. Silymarin dose-dependently inhibited
both cytokine-induced NO production and cell death in RINm5F cells, and
prevented IL-1b- and IFN-g-induced NO production and b-cell dysfunction in
human pancreatic islets [74].
In vivo studies on saponins isolated from Bupleurum rotundifolium L. (Apiaceae)
were reported to have anti-inflammatory activity against both TPA-induced ear
oedema and chronic skin inflammation [75]. Kim et al. suggested that the antiinflammatory activity of these saponins is related to anticomplementary action
through the classical inflammation pathway [76]. Tumor promoters induce TNF-a,
which stimulates the production of cell adhesion molecules. EGCG inhibited NF-kΒ
and expression of TNF-a, thereby reducing cancer promotion [77].
2.3 Anticancer Effect
Curcumin has been studied in multiple human carcinomas including melanoma,
head and neck, breast, colon, pancreatic, prostate, and ovarian cancers [13, 17].
Curcumin has been shown to inhibit the cyclins involved in cell cycle regulation.
Specifically, curcumin upregulates the expression of apoptotic gene p53, thus
inducing apoptosis at the G2 phase; the expression of Bax, thus initiating the
mitochondrial apoptotic pathway; and also promotes binding of TNF-a and Fas
ligand (death activators) to their corresponding cell surface receptors, thus
stimulating extrinsic apoptotic pathways [78].
Regulation of the cell cycle is one of the mechanisms of action of silymarin in
the prevention and therapeutic intervention of cancer. Silymarin has been reported
to suppress the proliferation of tumor cells in various cancers, including prostate
[79–81], ovarian [82], breast [83], lung [84], skin [73], and bladder [85]. Studies
demonstrate that silymarin arrests the cells at the G1 and G2/M phase, induces CDK
inhibitors (Cip1/p21 and Kip1/p27) and alters the expression of cyclin D kinases
[73]. Silymarin treatment has been shown to inhibit the growth of androgendependent (LNCaP) and androgen-independent (PC3 and DU145) prostate cancer
cells [39]. Apoptosis or programmed cell death that occurs in various physiological
and pathological conditions is one of the hallmarks of cancer. Several
phytochemicals that are known to inhibit NF-kB, and AP-1 activation can suppress
Phytomedicine-Loaded Polymeric Nanomedicines: Potential Cancer Therapeutics
211
arachadonic acid pathway for eicosanoid biosynthesis is an important participant
in the inflammatory response, generating a host of reactive lipid products including
leukotrienes, prostaglandins, prostacyclins, and thromboxanes. Curcumin has been
shown to decrease the metabolism of arachadonic acid by downregulating the
activity of LOX and COX-2, both at the transcriptional level as well as via posttranslational enzyme inhibition. Curcumin inhibited prostaglandin E2 biosynthesis
through direct inhibition of the microsomal prostaglandin E2 synthase-1 enzyme.
Studies have demonstrated that silymarin is a potent inhibitor of NF-kB activation in response to TNF-a. This effect was mediated through the inhibition of
phosphorylation and degradation of IkB [73]. Silymarin dose-dependently inhibited
both cytokine-induced NO production and cell death in RINm5F cells, and
prevented IL-1b- and IFN-g-induced NO production and b-cell dysfunction in
human pancreatic islets [74].
In vivo studies on saponins isolated from Bupleurum rotundifolium L. (Apiaceae)
were reported to have anti-inflammatory activity against both TPA-induced ear
oedema and chronic skin inflammation [75]. Kim et al. suggested that the antiinflammatory activity of these saponins is related to anticomplementary action
through the classical inflammation pathway [76]. Tumor promoters induce TNF-a,
which stimulates the production of cell adhesion molecules. EGCG inhibited NF-kΒ
and expression of TNF-a, thereby reducing cancer promotion [77].
2.3 Anticancer Effect
Curcumin has been studied in multiple human carcinomas including melanoma,
head and neck, breast, colon, pancreatic, prostate, and ovarian cancers [13, 17].
Curcumin has been shown to inhibit the cyclins involved in cell cycle regulation.
Specifically, curcumin upregulates the expression of apoptotic gene p53, thus
inducing apoptosis at the G2 phase; the expression of Bax, thus initiating the
mitochondrial apoptotic pathway; and also promotes binding of TNF-a and Fas
ligand (death activators) to their corresponding cell surface receptors, thus
stimulating extrinsic apoptotic pathways [78].
Regulation of the cell cycle is one of the mechanisms of action of silymarin in
the prevention and therapeutic intervention of cancer. Silymarin has been reported
to suppress the proliferation of tumor cells in various cancers, including prostate
[79–81], ovarian [82], breast [83], lung [84], skin [73], and bladder [85]. Studies
demonstrate that silymarin arrests the cells at the G1 and G2/M phase, induces CDK
inhibitors (Cip1/p21 and Kip1/p27) and alters the expression of cyclin D kinases
[73]. Silymarin treatment has been shown to inhibit the growth of androgendependent (LNCaP) and androgen-independent (PC3 and DU145) prostate cancer
cells [39]. Apoptosis or programmed cell death that occurs in various physiological
and pathological conditions is one of the hallmarks of cancer. Several
phytochemicals that are known to inhibit NF-kB, and AP-1 activation can suppress
Phytomedicine-Loaded Polymeric Nanomedicines: Potential Cancer Therapeutics
211