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

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.

Acknowledgments

The authors acknowledge the collaboration of the Endocrinology, Pathology and Surgery Departments from IPOLFG and Dr. Humberto Gonçalves from the Pharmacy of IPOLFG, for providing the chemotherapeutic drugs. iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is co-funded by FCT/MCES, through national funds, and by FEDER under the PT2020 Partnership Agreement, is also acknowledged.

Disclosure Statement

The authors declare no conflicts of interest.

Additional information

Funding

This work was supported by Associação de Endocrinologia Oncológica (AEO) and iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is co-funded by Fundação para a Ciência e Tecnologia/Ministério da Ciência e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement. Núcleo Regional Sul da Liga Portuguesa Contra o Cancro (NRS-LPCC) granted the researcher Marta Pojo.

Notes on contributors

Diana P. Sousa

B.M.C., M.P., A.T.P., and D.P.S. conceived the experiments. D.P.S., M.P., and A.T.P. performed the experiments, collected and analyzed data. B.M.C. and A.T.S. analyzed data and provided materials and resources. D.P.S. wrote the manuscript, with contribution from the other authors. D.P.S., M.P., A.T.P., V.L., A.T.S., and B.M.C. reviewed the manuscript.

Marta Pojo

B.M.C., M.P., A.T.P., and D.P.S. conceived the experiments. D.P.S., M.P., and A.T.P. performed the experiments, collected and analyzed data. B.M.C. and A.T.S. analyzed data and provided materials and resources. D.P.S. wrote the manuscript, with contribution from the other authors. D.P.S., M.P., A.T.P., V.L., A.T.S., and B.M.C. reviewed the manuscript.

Ana T. Pinto

B.M.C., M.P., A.T.P., and D.P.S. conceived the experiments. D.P.S., M.P., and A.T.P. performed the experiments, collected and analyzed data. B.M.C. and A.T.S. analyzed data and provided materials and resources. D.P.S. wrote the manuscript, with contribution from the other authors. D.P.S., M.P., A.T.P., V.L., A.T.S., and B.M.C. reviewed the manuscript.

Valeriano Leite

B.M.C., M.P., A.T.P., and D.P.S. conceived the experiments. D.P.S., M.P., and A.T.P. performed the experiments, collected and analyzed data. B.M.C. and A.T.S. analyzed data and provided materials and resources. D.P.S. wrote the manuscript, with contribution from the other authors. D.P.S., M.P., A.T.P., V.L., A.T.S., and B.M.C. reviewed the manuscript.

Ana Teresa Serra

B.M.C., M.P., A.T.P., and D.P.S. conceived the experiments. D.P.S., M.P., and A.T.P. performed the experiments, collected and analyzed data. B.M.C. and A.T.S. analyzed data and provided materials and resources. D.P.S. wrote the manuscript, with contribution from the other authors. D.P.S., M.P., A.T.P., V.L., A.T.S., and B.M.C. reviewed the manuscript.

Branca M. Cavaco

B.M.C., M.P., A.T.P., and D.P.S. conceived the experiments. D.P.S., M.P., and A.T.P. performed the experiments, collected and analyzed data. B.M.C. and A.T.S. analyzed data and provided materials and resources. D.P.S. wrote the manuscript, with contribution from the other authors. D.P.S., M.P., A.T.P., V.L., A.T.S., and B.M.C. reviewed the manuscript.