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

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.

The Effect of Resveratrol or Curcumin on Head and Neck Cancer Cells Sensitivity to the Cytotoxic Effects of Cisplatin

“…The solutions stock were filtered through a 0.22 μm membrane, aliquoted and stored at −20 °C until further use. The cisplatin, curcumin or resveratrol stock was used to obtain the working concentrations related to the treatment by performing dilutions in the culture medium [ 47 ].…”

Ciprofloxacin-Collagen-Based Materials with Potential Oral Surgical Applications

“…The collagen-based materials with identical mass were introduced in the culture mediums of Vascular Cell Basal Medium (ATCC PCS–100030) with HUVEC viable cells. After 6 h, 24 h, and respectively 48 h, the solid materials were pull out from de mediums, and the numbers of viable cells were quantified using the MTT method [ 38 , 42 , 43 , 44 , 45 ]. All determinations have been done in plates of 96 wells, in triplicate, each determination being performed for 3 times.…”

Therapeutic Potential of the Natural Compound S-Adenosylmethionine as a Chemoprotective Synergistic Agent in Breast, and Head and Neck Cancer Treatment: Current Status of Research

“…Curcumin has received great interest in the past two decades due to its biofunctional properties such as anticancer, antioxidant, and anti-inflammatory activities [ 64 , 65 ]. In FaDu and PE/CA PJ49 HNSCC cell lines curcumin potentiated the apoptotic process induced by cDDP by modulating ERK1/2 phosphorylation and lowered the required dose of the drug to 10 μM thus reducing its toxic adverse reactions [ 89 ]. In Hep2 human squamous laryngeal cancer cells curcumin enhanced the chemotherapeutic action of 25 μM cisplatin through activation of TRPM2 channel and mitochondrial oxidative stress and reduced cisplatin-induced drug resistance [ 90 ].…”