TY - JOUR
T1 - Nobiletin Alone or in Combination with Cisplatin Decreases the Viability of Anaplastic Thyroid Cancer Cell Lines
AU - Sousa, Diana P.
AU - Pojo, Marta
AU - Pinto, Ana T.
AU - Leite, Valeriano
AU - Serra, Ana Teresa
AU - Cavaco, Branca M.
N1 - This work was supported by Associacao de Endocrinologia Oncologica (AEO) and iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is co-funded by Fundacao para a Ciencia e Tecnologia/Ministerio da Ciencia e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement. Nucleo Regional Sul da Liga Portuguesa Contra o Cancro (NRS-LPCC) granted the researcher Marta Pojo.
PY - 2020/2/17
Y1 - 2020/2/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85068744051&partnerID=8YFLogxK
U2 - 10.1080/01635581.2019.1634745
DO - 10.1080/01635581.2019.1634745
M3 - Article
C2 - 31287730
AN - SCOPUS:85068744051
SN - 0163-5581
VL - 72
SP - 352
EP - 363
JO - Nutrition and Cancer
JF - Nutrition and Cancer
IS - 2
ER -
