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

Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Professor Lima Basto, Lisboa, Portugal. Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Professor Lima Basto, Lisboa, Portugal. iBET, Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal. Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa (ITQB NOVA), Oeiras, Portugal.

Nutrition and cancer. 2020;(2):352-363
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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.