Tamoxifen triggers apoptosis of papillary thyroid cancer cells by two different mechanisms

• Published in: Gene reports 2021-09, Vol.24, p.101266, Article 101266
• Main Authors: Dehghan, Mohammad Hossein, Hedayati, Mehdi, Shivaee, Setareh, Shakib, Heewa, Rajabi, Sadegh
• Format: Article
• Language: English
• Subjects: Apoptosis; LncRNA; Papillary thyroid cancer; Tamoxifen
• ISSN: 2452-0144; 2452-0144
• DOI: 10.1016/j.genrep.2021.101266

Thyroid cancer occurs more frequently in women, implying the probable role of female sex hormones in this high incidence. Tamoxifen is an anticancer drug that binds to estrogen receptor and antagonizes estrogen biological effects. The main goal of the current investigation was to identify the impact of tamoxifen on apoptosis of human papillary thyroid carcinoma (PTC) cell line, BCPAP, and clarify underlying mechanisms. BCPAP cell line was incubated with the 2.5 μM tamoxifen for 48 h. The proliferation of these cells was assayed utilizing 3-(4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) method. Then, the mRNA expression of antiapoptotic factor Bcl-2, pro-apoptotic factor BAX, Caspase-3, proliferation marker MKI67, as well as the expression of long non-coding RNAs TUG1, NEAT1, and lincDUSP were analyzed via Real time-polymerase chain reaction (Real time-PCR) technique. The expression of the caspase-3 protein was semi-quantified using western blotting. Tamoxifen hindered the proliferation of BCPAP cells and reduced the expression of proliferation marker MKI67. Tamoxifen induced apoptosis and decreased the expression of Bcl-2, while upregulated Bax and caspase-3 in BCPAP cells. It was also identified that TUG1, NEAT1, and lincDUSP expressions were downregulated by tamoxifen treatment. Tamoxifen blocked proliferation and stimulated apoptosis in the BCPAP cell line. A potential molecular mechanism was the stimulation of mitochondrial apoptosis via effects on MKI67, Bcl-2, Bax, and Caspase-3 expression. The other mechanism might function through downregulating TUG1, NEAT1, and lincDUSP. Thus, tamoxifen may provide a candidate for the development of a prospective therapeutic strategy for thyroid cancer. •Tamoxifen treatment of BCPAP cells significantly blocked their proliferation.•Tamoxifen probably targeted intrinsic pathway of apoptosis to kill BCPAP cells.•Anti-apoptotic lncRNAs may have a role in tamoxifen-induced apoptosis.