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Assessment of antiproliferative and apoptosis effects of liposomal formulation DODAC associated with synthetic phosphoethanolamine in cell lines of oral squamous cell carcinoma

Grant number: 15/00547-5
Support type:Scholarships in Brazil - Master
Effective date (Start): May 01, 2015
Effective date (End): April 30, 2017
Field of knowledge:Health Sciences - Dentistry
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Durvanei Augusto Maria
Grantee:Larissa Kim Higashi de Carvalho
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The head and neck squamous cell carcinoma account for approximately 10% of malignant tumors and 40% of these are manifested in the oral cavity, 90% correspond histologically to squamous cell carcinoma. The major carcinogenic agents related to oral cancer are tobacco, alcohol, radiation and some viruses. Clearly the risk of oral cancer is related to the intensity and duration of alcohol and tobacco use. In this project will be evaluated the antiproliferative and apoptosis properties in vitro of liposomal formulation DODAC associated with synthetic phosphoethanolamine (PHO-S) in two cell lines of human squamous cell carcinoma, SCC-9 and SCC-25. The phosphoethanolamine studied and developed by our group is a compound that is part of the alkyl phospholipid which has an inhibitory potential in B16F10 melanoma cells, causing no effects on normal cells and leads to cell cycle arrest in the G0 / G1 phases and increases significantly population of dead cells in sub-G1 possibly by apoptosis. In in vivo models PHO-S increased animal survival rate treated without significant side effects such as cachexia and myelosuppression, and drastically decrease formation of metastases. Treatment of oral cancer is onerous, long and requires monitoring by a multidisciplinary team. Surgery is the treatment of choice, which implies sequelae related to aesthetics, breath, speech, and chewing beyond patients have impaired social life. Chemotherapeutic have serious adverse effects and generally depress bone marrow, decreased growth, cause sterility, hair loss and can be teratogenic. The use of liposomes as chemotherapeutic vector opens great perspectives for the treatment of cancer, as they allow for greater efficiency, reducing toxicity and dosage of anticancer drug. The antiproliferative effects and apoptosis induction in this project will be evaluated by the MTT colorimetric assay, by the formation of free radicals lipoperoxides, by changes in cell death pathways by apoptosis and necrosis of squamous cell carcinoma SCC-9 and SCC-25 of cavity oral. The toxicity of synthetic phosphoethanolamine will also be analyzed for the expression of markers and cell signaling proteins by flow cytometry; intraestrutural changes by scanning electron microscopy and confocal laser. (AU)