Nobiletin Alone or in Combination with Cisplatin Decreases the Viability of Anaplastic Thyroid Cancer Cell Lines

Diana P Sousa1, Marta Pojo1, Ana T Pinto1

  • 1Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Professor Lima Basto, Lisboa, Portugal.

Nutrition and Cancer
|July 10, 2019
PubMed

Insights

Nobiletin, a compound from orange peels, shows promise in fighting aggressive anaplastic thyroid cancer (ATC). It effectively reduced cancer cell viability with less toxicity to normal cells, suggesting potential as a novel therapeutic strategy.

Area of Science:

  • Oncology
  • Pharmacology
  • Nutraceutical Research

Background:

  • Anaplastic thyroid cancer (ATC) is a highly aggressive thyroid cancer subtype with limited treatment options and high mortality.
  • Nutraceuticals, natural compounds with health benefits, have demonstrated anticancer properties, but their efficacy against ATC remains under-investigated.
  • Novel therapeutic strategies are urgently needed to improve outcomes for patients with anaplastic thyroid cancer.

Purpose of the Study:

  • To investigate the potential anticancer effects of specific nutraceuticals, including isothiocyanates (ITCs) and polymethoxylated flavones (PMFs), on anaplastic thyroid cancer cell lines.
  • To compare the efficacy and toxicity of these nutraceuticals against conventional chemotherapy drugs in ATC models.
  • To evaluate the combined effects of selected nutraceuticals with conventional treatments for enhanced therapeutic outcomes.

Main Methods:

  • Determined the half-maximal inhibitory concentration (IC50) values for ITCs (sulforaphane, phenethyl isothiocyanate) and PMFs (nobiletin, orange peel extract) in ATC (T235, T238) and normal thyroid (PCCL3) cell lines.
  • Assessed the impact of phenethyl isothiocyanate (PEITC) and nobiletin on cell viability and cell cycle progression.
  • Evaluated the efficacy of nobiletin and PEITC, individually and in combination with conventional drugs like cisplatin, on ATC cell viability.

Main Results:

  • Isothiocyanates demonstrated greater reduction in ATC metabolic viability compared to polymethoxylated flavones.
  • Nobiletin significantly decreased anaplastic thyroid cancer cell viability in a dose-dependent manner, comparable to cisplatin at 100 μM, with reduced toxicity to normal thyroid cells.
  • The combination of nobiletin (1 μM) and cisplatin resulted in enhanced reduction of T235 cell viability compared to either agent alone.

Conclusions:

  • Nobiletin exhibits significant dose-dependent cytotoxic effects against anaplastic thyroid cancer cells.
  • Nobiletin demonstrates a favorable therapeutic index, showing efficacy comparable to cisplatin but with lower toxicity to normal thyroid cells.
  • Nobiletin represents a promising candidate for further investigation as a potential therapeutic agent in the treatment of anaplastic thyroid cancer.

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