PC-SPES inhibits colon cancer growth in vitro and in vivo

Sergio Huerta, James R. Arteaga, Ronald W. Irwin, Takayuki Ikezoe, David Heber, H. Phillip Koeffler

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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 Apcmin 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 ≤ 0.3% (v/v)]. PC-SPES resulted in a marked suppression of cell proliferation in all colon cancer cells studied. PC-SPES (3 μl/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 (≥60%) accumulation of cells in the G2-M phase with a comitant decrease of cells in the G0-G1 phase in all colon cancer cell lines studied after treatment with PC-SPES (1.5 μl/ml for 48 h). Western blot analysis demonstrated a decrease in protein levels of β-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 Apcmin 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 Apcmin 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.

Original languageEnglish (US)
Pages (from-to)5204-5209
Number of pages6
JournalCancer Research
Volume62
Issue number18
StatePublished - Sep 15 2002

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Colonic Neoplasms
Growth
Cell Line
Prostatic Neoplasms
herbal preparation PC-SPES
In Vitro Techniques
Neoplasms
Cell Proliferation
Cell Cycle Resting Phase
Carboxymethylcellulose Sodium
DNA Nucleotidylexotransferase
Polysorbates
G2 Phase
G1 Phase
Tubulin
Polyps
Cell Cycle Checkpoints
Tumor Burden
Cell Division
Gastrointestinal Tract

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Huerta, S., Arteaga, J. R., Irwin, R. W., Ikezoe, T., Heber, D., & Koeffler, H. P. (2002). PC-SPES inhibits colon cancer growth in vitro and in vivo. Cancer Research, 62(18), 5204-5209.

PC-SPES inhibits colon cancer growth in vitro and in vivo. / Huerta, Sergio; Arteaga, James R.; Irwin, Ronald W.; Ikezoe, Takayuki; Heber, David; Koeffler, H. Phillip.

In: Cancer Research, Vol. 62, No. 18, 15.09.2002, p. 5204-5209.

Research output: Contribution to journalArticle

Huerta, S, Arteaga, JR, Irwin, RW, Ikezoe, T, Heber, D & Koeffler, HP 2002, 'PC-SPES inhibits colon cancer growth in vitro and in vivo', Cancer Research, vol. 62, no. 18, pp. 5204-5209.
Huerta S, Arteaga JR, Irwin RW, Ikezoe T, Heber D, Koeffler HP. PC-SPES inhibits colon cancer growth in vitro and in vivo. Cancer Research. 2002 Sep 15;62(18):5204-5209.
Huerta, Sergio ; Arteaga, James R. ; Irwin, Ronald W. ; Ikezoe, Takayuki ; Heber, David ; Koeffler, H. Phillip. / PC-SPES inhibits colon cancer growth in vitro and in vivo. In: Cancer Research. 2002 ; Vol. 62, No. 18. pp. 5204-5209.
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abstract = "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 Apcmin 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 ≤ 0.3{\%} (v/v)]. PC-SPES resulted in a marked suppression of cell proliferation in all colon cancer cells studied. PC-SPES (3 μl/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 (≥60{\%}) accumulation of cells in the G2-M phase with a comitant decrease of cells in the G0-G1 phase in all colon cancer cell lines studied after treatment with PC-SPES (1.5 μl/ml for 48 h). Western blot analysis demonstrated a decrease in protein levels of β-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 Apcmin 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 Apcmin 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.",
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N2 - 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 Apcmin 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 ≤ 0.3% (v/v)]. PC-SPES resulted in a marked suppression of cell proliferation in all colon cancer cells studied. PC-SPES (3 μl/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 (≥60%) accumulation of cells in the G2-M phase with a comitant decrease of cells in the G0-G1 phase in all colon cancer cell lines studied after treatment with PC-SPES (1.5 μl/ml for 48 h). Western blot analysis demonstrated a decrease in protein levels of β-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 Apcmin 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 Apcmin 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.

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