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Updated: Jan 22, 2026

Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
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.
Abstract:
Aim: Anaplastic thyroid cancer (ATC) is the most aggressive subtype of thyroid cancer, presenting high mortality. Currently, no curative treatments exist and new therapeutic strategies are required. Although nutraceuticals were reported to have anticancer properties, few studies exist on ATC. This study aimed to investigate the anticancer effects of nutraceuticals in ATC cell lines (T235, T238) in comparison with normal thyroid cells (PCCL3).Methods: The IC50 values of isothiocyanates (ITCs: sulforaphane, SFN; phenethyl isothiocyanate, PEITC) and polymethoxylated flavones (PMFs: nobiletin; orange peel extract, OPE) were determined. ITCs decreased ATC metabolic viability more efficiently than PMFs. The effects of PEITC and nobiletin on viability and cell cycle, alone or in combination with conventional drugs, were evaluated.Results: PEITC did not affect viability of normal thyroid and ATC cells, while nobiletin decreased viability in a dose-dependent manner in all cell lines, although cell cycle was not arrested. At 100 μM, nobiletin reduced ATC cell viability as efficiently as conventional drugs, such as cisplatin, while being less toxic to normal thyroid cells. When conjugated with 1 μM cisplatin, the combination decreased viability of T235 cells more efficiently than each compound alone.Conclusion: These results suggest nobiletin as a potential anticancer agent that warrants further investigation in ATC.
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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