Vorinostat-loaded titanium oxide nanoparticles (anatase) induce G2/M cell cycle arrest in breast cancer cells via PALB2 upregulation

载有伏立诺他的二氧化钛纳米粒子(锐钛矿)通过上调 PALB2 诱导乳腺癌细胞 G2/M 细胞周期停滞

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作者:Shaimaa Abdel-Ghany, Sara Raslan, Huseyin Tombuloglu, Aly Shamseddin, Emre Cevik, Osama A Said, Engy F Madyan, Mehmet Senel, Ayhan Bozkurt, Suriya Rehman, Hussein Sabit

Abstract

Breast cancer is a group of diseases in which cells divide out of controlled, typically resulting in a mass. Erlotinib is targeted cancer drug which functions as an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. It is used mainly to treat of non-small cell lung cancer patients and has an action against pancreatic cancer. Vorinostat (aka suberanilohydroxamic acid) is an inhibitor of histone deacetylases (HDAC), which has an epigenetic modulation activity. It is used to treat cutaneous T cell lymphoma. In the present study, the erlotinib (ERL) and vorinostat (SAHA) loaded TiO2 nanoparticles (NPs) were used for the treatment of the breast cancer cells (MDA-MB-231 and MCF-7) and human cancerous amniotic cells (WISH). Cell count and viability were negatively affected in all treatments compared to normal cells and bare TiO2 NPs. Apoptosis results indicated a significant increase in the total apoptosis in all treatments compared with control cells. ERL- and SAHA-loaded TiO2 NPs treatments arrested breast cancer cells at G2/M phase, which indicate the cytotoxic effect of these treatment. Partner and localizer of BRCA2 (PALB2) gene expression was assessed using qPCR. The results indicate that PLAB2 was upregulated in ERL- and SAHA-loaded TiO2 NPs compared with control cells and can be used as nanocarrier for chemotherapy drugs. However, this conclusion necessitates further confirmative investigation.

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