Medicinal Plants Classification Biosynthesis and ... - Index of

150
Hua-Bin Li, Dan Li, Ren-You Gan et al.
subfamilies. Baicalin did not interact with CX3C chemokine fractalkine/neurotactin or other
cytokines, such as TNF-alpha and IFN-gamma, indicating that its action was selective. One
possible anti-inflammatory mechanism of baicalin was to bind a variety of chemokines and
limit their biological function [Li et al., 2000a].
6.3. Anticancer Effects
S. baicalensis exerted dose- and time-dependent growth inhibition to two human prostate
cancer cell lines (LNCaP, androgen dependent, and PC-3, androgen independent). However,
the PC-3 cells were slightly more sensitive than LNCaP cells, although the former is
androgen independent. Significant reduction of prostaglandin E-2 (PGE2) synthesis in both
cells after treatment with S. baicalensis resulted from direct inhibition of COX-2 activity
rather than COX-2 protein suppression. S. baicalensis also inhibited prostate-specific antigen
production in LNCaP cells. Finally, S. baicalensis suppressed expression of Cyclin DI in
LNCaP cells, resulting in a G(1) phase arrest, while inhibiting Cdk1 expression and kinase
activity in PC-3 cells, ultimately leading to a G(2)/M cell cycle arrest. Animal studies showed
a 50% reduction in tumor volume after a 7-wk treatment period [Ye et al., 2007].
Furthermore, four compounds (baicalein, wogonin, neobaicalein and skullcapflavone)
capable of inhibiting prostate cancer cell proliferation were separated and identified from S.
baicalensis. Comparisons of the cellular effects induced by the entire extract versus the fourcompound
combination produced comparable cell cycle changes, levels of growth inhibition,
and global gene expression profiles (r 2 = 0.79). Individual compounds exhibited
antiandrogenic activities with reduced expression of the androgen receptor and androgenregulated
genes. In vivo, baicalein (20 mg/kg/d p.o.) reduced the growth of prostate cancer
xenografts in nude mice by 55% at 2 weeks compared with placebo [Bonham et al., 2005].
In order to study anticancer activity of S. baicalensis on head and neck squamous cell
carcinoma (HNSCC) in vitro and in vivo and to investigate its effect on COX-2, which
converts arachidonic acid to PGE2 and is highly expressed in HNSCC, two human HNSCC
cell lines (SCC-25 and KB) and a nontumorigenic cell line (HaCaT) were tested in vitro for
growth inhibition, proliferation cell nuclear antigen expression, and COX-2 activity and
expression after treatment with its extract. S. baicalensis, indomethacin (a nonselective COX
inhibitor) and celecoxib (a selective COX-2 inhibitor) demonstrated a strong growth
inhibition in both tested human HNSCC cell lines. No growth inhibition of HaCaT cells was
observed with S. baicalensis. The IC50s were 150 g/ml for Scutellaria baicalensis, 25 M
for celecoxib, and 75 M for baicalein and indomethacin. S. baicalensis as well as celecoxib
and indomethacin, but not baicalein, suppressed proliferation cell nuclear antigen expression
and PGE2 synthesis in both cell types. S. baicalensis inhibited COX-2 expression, whereas
celecoxib inhibited COX-2 activity directly. A 66% reduction in tumor mass was observed in
the nude mice by S. baicalensis, which selectively and effectively inhibited cancer cell
growth in vitro and in vivo and could be an effective chemotherapeutic agent for HNSCC.
Inhibition of PGE2 synthesis via suppression of COX-2 expression might be responsible for
its anticancer activity. Differences in biological effects of S. baicalensis compared with
baicalein suggested the synergistic effects among components in S. baicalensis [Zhang et al.,