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PPARgamma Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention: A Pilot Study

Hirokazu Takahashi1, Kunihiro Hosono, Takashi Uchiyama

  • 1Gastroenterology Division, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan.

PPAR Research
|September 4, 2010
PubMed

Insights

Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma) ligand, significantly reduced aberrant crypt foci (ACF), a colorectal cancer risk marker. This pilot study suggests pioglitazone

Area of Science:

  • Oncology
  • Pharmacology
  • Gastroenterology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands, like pioglitazone, are used for diabetes and show potential in inhibiting colorectal cancer (CRC).
  • Aberrant crypt foci (ACF) are validated biomarkers for CRC risk in animal models and can be detected in humans, serving as a surrogate marker for CRC chemoprevention studies.
  • ACF evaluation offers a shorter timeframe for assessing chemopreventive agents compared to traditional CRC and adenoma endpoints.

Purpose of the Study:

  • To investigate the chemopreventive effect of pioglitazone on the development of human aberrant crypt foci (ACF).
  • To assess pioglitazone's impact on ACF as a surrogate marker for colorectal cancer (CRC) chemoprevention.

Main Methods:

  • A pilot clinical study involving 29 patients, divided into a control group (n=20) and a pioglitazone treatment group (n=9).
  • Patients received 15 mg/day of pioglitazone for 1 month.
  • Aberrant crypt foci (ACF) and adenomas were examined endoscopically before and after the treatment period.

Main Results:

  • A significant decrease in the number of ACF was observed after 1 month of pioglitazone treatment (from 5.8 ± 1.1 to 3.3 ± 2.3).
  • No significant changes were noted in the number of crypts per ACF or in the number and size of adenomas.
  • Pioglitazone demonstrated a reduction in ACF, indicating a potential chemopreventive effect.

Conclusions:

  • Pioglitazone may hold clinical utility as a colorectal cancer-preventive drug.
  • The reduction in ACF suggests pioglitazone's potential as a chemopreventive agent for colorectal carcinogenesis.
  • Further clinical studies are warranted to confirm the efficacy of PPARgamma ligands, such as pioglitazone, in colorectal cancer prevention.

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