Cisplatin effect on head and neck squamous cell carcinoma cells is modulated by ERK1/2 protein kinases

Marinela Bostan; Georgiana Gabriela Petrică-Matei; Gabriela Ion; Nicoleta Radu; Mirela Mihăilă; Răzvan Hainăroşie; Lorelei Irina Braşoveanu; Viviana Roman; Carolina Constantin; Monica Teodora Neagu

doi:10.3892/etm.2019.8139

Cisplatin effect on head and neck squamous cell carcinoma cells is modulated by ERK1/2 protein kinases

Exp Ther Med. 2019 Dec;18(6):5041-5051. doi: 10.3892/etm.2019.8139. Epub 2019 Oct 25.

Affiliations

¹ 'Stefan S. Nicolau' Institute of Virology, Center of Immunology, 030304 Bucharest, Romania.
² Department of Immunology, 'Victor Babeș' National Institute of Pathology, 050096 Bucharest, Romania.
³ Department of Cytogenetics, Personal Genetics - Medical Genetics Center, 010987 Bucharest, Romania.
⁴ Department of Biotechnology, University of Agronomic Sciences and Veterinary Medicine of Bucharest, 011464 Βucharest, Romania.
⁵ Biotechnology Department and National Institute for Chemistry and Petrochemistry R&D of Bucharest, 060021 Bucharest, Romania.
⁶ 'Prof. Dr. Dorin Hociotă' Institute of Phonoaudiology and Functional ENT Surgery, 061344 Bucharest, Romania.

Abstract

The extracellular signal-regulated kinases (ERKs) are key transducers of the extracellular signals into intracellular responses and represent major molecular players in tumorigenesis. The aim of this study was to determine how curcumin (CRM) used as an adjuvant supports the apoptotic process induced by a single chemical agent treatment (cisplatin-CisPT) on two head and neck squamous cell carcinoma cell lines (FaDu and PE/CA-PJ49) and the involvement of ERK1/2 and/or p53 activation in this process. Data have shown that the CisPt effect is potentiated by CRM. CRM induced an increase of p53 protein phosphorylation in both cell lines. CisPt decreased p53 protein phosphorylation in FaDu cells, but increased it in PE/CA-PJ49 cells. Data showed that the constitutive expression of activated ERK1/2 protein-kinase was different in the two analyzed tumor cell lines. ERK1/2 activation status was essential for both cell processes, proliferation and apoptosis induced by CisPt and/or CRM treatment on squamous cell carcinoma cells. Our data suggest that p53 phosphorylation in the apoptotic process induced by CRM treatment might require the involvement of ERK1/2. In this regard the CisPt treatment suggested that p53 phosphorylation is ERK1/2 independent in FaDu cells having a p53 gene deletion and ERK1/2 dependent in PE/CA-PJ49 cells having a p53 gene amplification. Moreover, in both tumor cell lines our results support the involvement of p53 phosphorylation-ERK1/2 activation-dependent in the apoptosis induced by combined treatments (CisPt and CRM). The use of CRM as adjuvant could increase the efficiency of chemotherapy by modulating cellular activation processes of ERK1/2 signaling pathways. In conclusion, the particular mode of intervention by which ERK1/2 might influence cell proliferation and/or apoptosis processes depends on the type of therapeutic agent, the cells' particularities, and the activation status of the ERK1/2.

Keywords: ERK1/2; apoptosis; cisplatin; curcumin; head and neck tumor cells; p53.