Preventive Potential of Resveratrol in Carcinogen-Induced Rat Thyroid Tumorigenesis

Nutrients. 2018 Feb 28;10(3):279. doi: 10.3390/nu10030279.

Abstract

Thyroid cancer (TC) is the most common endocrine malignancy without reliable preventive agent. Resveratrol possesses in vitro anti-TC activities; while its effect(s) on thyroid tumorigenesis remains unknown. This study aims to address this issue using DEN/MNU/DHPN-induced rat carcinogenesis model. 50 male Sprague-Dawley rats were separated into four groups as Group-1 (5 rats); normally fed; Group-2 (15 rats); DEN/MNU/DHPN treatment only; Group-3 (15 rats) and -4 (15 rats); DEN/MNU/DHPN treatment; followed by resveratrol intragastric (IG) injection and intraperitoneal (IP) injection; respectively; in two-day intervals for 30 weeks. The results revealed that the average resveratrol concentration in thyroid tissues was 1.278 ± 0.419 nmol/g in IG group and 1.752 ± 0.398 nmol/g in IP group. The final body weights of Group-3 and Group-4 were lighter than that (p > 0.05) of Group-1; but heavier than Group-2 (p < 0.05). TC-related lesions (hyperplasia and adenomas) were found in 53.3% of Group-2; 33.3% Group-3 and 26.7% Group-4. Lower serum carcino-embryonic antigen (CEA) and thyroglobulin (Tg) levels; down-regulated expression of IL-6 and cyclooxygenase-2 (COX-2); reduction of NF-κB/p65 nuclear translocation; and elevated IkBα expression were found in the thyroid tissues of Group-3 and Group-4 in comparison with that of Group-2. These results demonstrate that IG and IP administered resveratrol efficiently reduces the frequency and severity of DEN/MNU/DHPN-caused TC-related lesions and would be of values in thyroid tumor prevention.

Keywords: chemoprevention; resveratrol; thyroid tumorigenesis.

MeSH terms

  • Adenoma / blood
  • Adenoma / chemically induced
  • Adenoma / pathology
  • Adenoma / prevention & control*
  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Carcinoembryonic Antigen / blood
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / chemically induced
  • Cell Transformation, Neoplastic / drug effects*
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Cyclooxygenase 2 / metabolism
  • Diethylnitrosamine
  • Humans
  • Hyperplasia
  • Interleukin-6 / metabolism
  • Male
  • Methylnitrosourea
  • NF-KappaB Inhibitor alpha / metabolism
  • Nitrosamines
  • Rats, Sprague-Dawley
  • Resveratrol
  • Stilbenes / pharmacology*
  • Thyroglobulin / blood
  • Thyroid Gland / drug effects*
  • Thyroid Gland / metabolism
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / blood
  • Thyroid Neoplasms / chemically induced
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / prevention & control*
  • Time Factors
  • Transcription Factor RelA / metabolism

Substances

  • Anticarcinogenic Agents
  • Carcinoembryonic Antigen
  • Interleukin-6
  • Nfkbia protein, rat
  • Nitrosamines
  • Rela protein, rat
  • Stilbenes
  • Transcription Factor RelA
  • NF-KappaB Inhibitor alpha
  • Diethylnitrosamine
  • diisopropanolnitrosamine
  • Methylnitrosourea
  • Thyroglobulin
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Resveratrol