Abstract

Laryngeal squamous cell carcinoma (LSCC), is characterized by an aggressive clinical behavior and lack of specific targeted therapies. Thus, novel therapeutic approaches that take advantage of the combination of anticancer natural compounds and chemotherapeutic molecules currently used for LSCC are strongly necessary. S-adenosyl-L-methionine (AdoMet), the main biological methyl donor, is well known for its antiproliferative, proapoptotic and antimetastatic effect in several type of human cancer. In the current study we investigated the antitumor activity of AdoMet in combination with cisplatin (cDDP), an agent usually used in cancer therapy of LSCC, in JHU-SCC-011 cells and we explored the underlying mechanisms. We found that the combination of 200μM AdoMet/0.18μM cDDP synergistically enhanced apoptosis via intrinsic mechanism as confirmed by Western blot analysis of the main proteins involved in this process. Because escape from apoptosis and decreased activation of JNK and ERK are mechanisms of resistance to cDPP, the activation of ERK‐1/2 and JNK and the downregulation of the antiapoptotic Bcl-2 protein induced by combined treatments could represent the strategy utilized by AdoMet to potentiate the therapeutic effectiveness of cDDP. The overall data highlighted AdoMet and cisplatin combination as a potential therapy for LSCC in order to improve therapeutic efficacy by reducing side effects and drug resistance mechanisms.

Keywords: S-Adenosylmethionine; Laryngeal squamous cancer cells; Head and neck squamous cell carcinoma; Apoptosis; Cisplatin; Drug combination

Abbreviations: AdoMet: S-Adenosyl-L-Methionine; LSCC: Laryngeal Squamous Cell Carcinoma; HNSCC: Head and Neck Squamous Cell Carcinoma; MAPK: Mitogen-Activated Protein Kinase; JNK1: c-Jun N-Terminal Kinase; ERK1/2: Extracellular Signal-Regulated Kinase ½; PI: Propidium Iodide; PARP-1: Poly (ADP Ribose) Polymerase, Annexin V-FITC: Annexin V-Fluorescein Isothiocyanate; FACS : Fluorescence-Activated Cell Sorting; SD: Standard Deviation; cDDP: Cisplatin