Epigallocatechin-3-gallate suppresses cell proliferation and promotes apoptosis and autophagy in oral cancer SSC-4 cells

Alexandra Iulia Irimie,1 Cornelia Braicu,2 Oana Zanoaga,2 Valentina Pileczki,2,3 Claudia Gherman,2,4 Ioana Berindan-Neagoe,2,4–6 Radu Septimiu Campian7 1Department of Prosthodontics and Dental Materials, Faculty of Dental Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 3Department of Analytical Chemistry, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof Dr. Ion Chiricuta”, Cluj-Napoca, Romania; 5Department of Immunology, Faculty of Medicine, University of Medicine and Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 6Department of Experimental Therapeutics MD Anderson Cancer Center Houston, TX, USA; 7Department of Oral Rehabilitation, Faculty of Dental Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania Abstract: Epigallocatechin-3-gallate (EGCG) is the major bioactive component of green tea. Our experimental data indicated that EGCG treatment suppresses cell proliferation of SSC-4 human oral squamous cell carcinoma (OSCC), the effect being dose- and time-dependent. In parallel was observed the activation of apoptosis and autophagy, in response to EGCG exposure in SSC-4 cells. Treatment with EGCG activates the expression of the BAD, BAK, FAS, IGF1R, WNT11, and ZEB1 genes and inhibits CASP8, MYC, and TP53. All of these results suggest that EGCG has an excellent potential to become a therapeutic compound for patients with OSCC, by inducing tumor cell death via apoptosis and autophagy. Keywords: oral squamous carcinoma, time dependent cell proliferation, gene expressio

RNA interference: new mechanistic and biochemical insights with application in oral cancer therapy

Smaranda Buduru,1 Alina-Andreea Zimta,2 Cristina Ciocan,2 Cornelia Braicu,3 Diana Dudea,4 Alexandra Iulia Irimie,4 Ioana Berindan-Neagoe2,3,5 1Department of Prosthetics and Dental Materials, Faculty of Dental Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 2MEDFUTURE – Research Center for Advanced Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 3Research Center for Functional Genomics and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4Department of Prosthetic Dentistry and Dental Materials, Division Dental Propaedeutic, Aesthetic, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 5Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof Dr Ion Chiricuta”, Cluj-Napoca, Romania Abstract: Over the last few decades, the incidence of oral cancer has gradually increased, due to the negative influence of environmental factors and also abnormalities within the genome. The main issues in oral cancer treatment consist in surpassing resistance and recurrence. However, continuous discovery of altered signaling pathways in these tumors provides valuable information for the identification of novel gene candidates targeted in personalized therapy. RNA interference (RNAi) is a natural mechanism that involves small interfering RNA (siRNA); this can be exploited in biomedical research by using natural or synthetic constructs for activation of the mechanism. Synthetic siRNA transcripts were developed as a versatile class of molecular tools that have a diverse range of programmable roles, being involved in the regulation of several biological processes, thereby providing the perspective of an alternative option to classical treatment. In this review, we summarize the latest information related to the application of siRNA in oral malignancy together with molecular aspects of the technology and also the perspective upon the delivery system. Also, the emergence of newer technologies such as clustered regularly interspaced short palindromic repeats/Cas9 or transcription activator-like effector nucleases in comparison with the RNAi approach is discussed in this paper. Keywords: RNA interference, oral cancer, therapeutic strategy, mechanistic and biochemical insight

Future trends and emerging issues for nanodelivery systems in oral and oropharyngeal cancer

Alexandra Iulia Irimie,1 Laura Sonea,2 Ancuta Jurj,3 Nikolay Mehterov,4,5 Alina Andreea Zimta,2,3 Liviuta Budisan,3 Cornelia Braicu,3 Ioana Berindan-Neagoe2,3,6 1Department of Prosthodontics and Dental Materials, Faculty of Dental Medicine, 2MedFuture Research Center for Advanced Medicine, 3Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 4Department of Medical Biology, Medical University of Plovdiv, 5Technological Center for Emergency Medicine, Plovdiv, Bulgaria; 6Department of Functional Genomics and Experimental Pathology, Ion Chiricuta Oncology Institute, Cluj-Napoca, Romania Abstract: Oral cancer is a prevalent cancer type on a global scale, whose traditional treatment strategies have several drawbacks that could in the near future be overcome through the development of novel therapeutic and prognostic strategies. Nanotechnology provides an alternative to traditional therapy that leads to enhanced efficiency and less toxicity. Various nanosystems have been developed for the treatment of oral cancer, including polymeric, metallic, and lipid-based formulations that incorporate chemotherapeutics, natural compounds, siRNA, or other molecules. This review summarizes the main benefits of using these nanosystems, in parallel with a particular focus on the issues encountered in medical practice. These novel strategies have provided encouraging results in both in vitro and in vivo studies, but few have entered clinical trials. The use of nanosystems in oral cancer has the potential of becoming a valid therapeutic option for patients suffering from this malignancy, considering that clinical trials have already been completed and others are currently being developed. Keywords: oral cancer, nanoparticle, lipidic nanosystems, polymeric micelles, dendrimer