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Chemoprevention of Azoxymethane-induced Colon Carcinogenesis by Delta-Tocotrienol

Kazim Husain1, Anying Zhang1,2, Steve Shivers1

  • 1Gastrointestinal Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Cancer Prevention Research (Philadelphia, Pa.)
|April 4, 2019
PubMed

Insights

δ-tocotrienol (DT3), a vitamin E form, shows potent preclinical activity against colorectal cancer. DT3 selectively inhibits cancer cell growth, migration, and invasion while preventing tumor development in rats.

Area of Science:

  • Biochemistry
  • Oncology
  • Nutritional Science

Background:

  • Colorectal cancer (CRC) remains a significant health concern globally.
  • Vitamin E isomers, particularly tocotrienols, are investigated for their potential health benefits.
  • δ-tocotrienol (DT3) exhibits unique biological properties.

Purpose of the Study:

  • To evaluate the preclinical efficacy of δ-tocotrienol (DT3) in inhibiting colorectal cancer growth and development.
  • To assess the selective toxicity of DT3 towards colorectal cancer cells versus normal colon cells.
  • To investigate the molecular mechanisms underlying DT3's anti-cancer effects.

Main Methods:

  • In vitro studies using colorectal cancer cell lines (HCT-116, SW-620, HT-29) and normal colon cells (NCM460).
  • Assessment of cell proliferation, malignant transformation, migration, invasion, and apoptosis.
  • Analysis of key molecular markers associated with cancer progression (EMT, metastasis, angiogenesis, inflammation, Wnt signaling).
  • In vivo study using an azoxymethane-induced colorectal carcinogenesis model in rats.

Main Results:

  • DT3 significantly inhibited malignant transformation, migration, and invasion in colorectal cancer cells without affecting normal cells.
  • DT3 suppressed key cancer markers including E-cadherin, vimentin, MMP-9, VEGF, NF-κB, and β-catenin.
  • DT3 selectively induced apoptosis in colorectal cancer cells.
  • In rats, DT3 administration significantly reduced colorectal polyps by 70% and colorectal cancer by 99%.

Conclusions:

  • δ-tocotrienol (DT3) demonstrates significant preclinical chemopreventive and therapeutic potential against colorectal cancer.
  • DT3 exhibits selective toxicity towards cancer cells and inhibits multiple pathways crucial for tumor growth and metastasis.
  • These findings support further clinical investigation of DT3 for colorectal cancer prevention and treatment.

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