PC-SPES is a mixture of eight herbs with antiproliferative activity in
prostate cancer cell lines and antitumor effects in animal models of
prostate cancer. In addition, evidence of clinical efficacy in advanced
prostate cancer has been reported.
PC-SPES has also been shown to have antitumor activity against several other
cancer cell lines including breast and neuroepithelial
cancer,
melanoma, and
leukemia cell lines. Because of these findings, we investigated the effects of
PC-SPES in vitro in
colon cancer cell lines SW480, SW620, and DLD-1 and in vivo in the Apc(min) mouse, a murine model for intestinal
carcinogenesis. For the in vitro studies,
colon cancer cell lines were exposed to an ethanolic extract of
PC-SPES compared with a diluent control [
ethanol < or = 0.3% (v/v)].
PC-SPES resulted in a marked suppression of cell proliferation in all
colon cancer cells studied.
PC-SPES (3 micro l/ml) caused a 95% inhibition of cell proliferation of the DLD-1
colon cancer cell line, and similar results were observed in the SW480 and SW620
colon cancer cell lines. Cell cycle analysis demonstrated a drastic (> or =60%) accumulation of cells in the G(2)-M phase with a concomitant decrease of cells in the G(0)-G(1) phase in all
colon cancer cell lines studied
after treatment with
PC-SPES (1.5 micro l/ml for 48 h). Western blot analysis demonstrated a decrease in
protein levels of
beta-tubulin in the SW620 cell line exposed to
PC-SPES.
Terminal deoxynucleotidyl transferase-mediated nick end labeling analysis revealed an increase in apoptotic
colon cancer cells incubated with
PC-SPES. For the in vivo studies, female 4-5-week-old Apc(min) mice were randomized to two groups: a
PC-SPES-treated group (n = 11) received 250 mg/kg/day (0.2 ml)
PC-SPES via gastrointestinal gavage; and a control group (n = 10) received 0.2 ml of the vehicle
solution (1.5%
carboxymethylcellulose with 0.2%
Tween 20) via gastrointestinal gavage. Both groups were treated five times a week for 10 weeks.
After treatment, the gastrointestinal tract was dissected for
polyp scoring by two observers blinded to treatment. The Apc(min) mice given
PC-SPES had a 58% reduction in
tumor number and a 56% decrease in
tumor load. No effect on either food intake or
body weight was observed in the treated versus
sham groups. The present study is the first to report the potent activity of
PC-SPES against
colon cancer. Both cell cycle arrest and apoptosis occurred
after treatment with
PC-SPES. This suggests that the components of this herbal mixture, either independently or in combination, acted in
colon cancer, resulting in a drastic effect on
tumor initiation and
tumor progression.