Evaluation of in vitro response to treatment with Melittin from Apis mellifera venom in cancer stem cells of canine osteosarcoma

• Grant number: 23/00973-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2024
• End date: June 30, 2024
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Renee Laufer Amorim
• Grantee: Giovana Pedro
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 21/11936-3 - Center for Translational Science and Biopharmaceutical Development, AP.CCD

Abstract

Canine osteosarcoma accounts for approximately 80% of primary malignant bone tumors. It is a tumor of mesenchymal origin, with malignant cells of osteoblastic differentiation. They are classified as central or medullary, peripheral or periosteal, with central or medullary being the most predominant (80%). It occurs mainly in long bones (75%), where it is more aggressive. The etiology is still not fully elucidated, but it is suggested that multiple microtraumas in the metaphyseal region, chronic inflammation, large dogs and diet in addition to genetic factors are related. It has a high capacity for local aggression, in addition to causing bone destruction, it can also cause regional and distant metastases. The treatment of choice consists of amputation and adjuvant chemotherapy. The average survival time of dogs with appendicular osteosarcoma treated with amputation alone is approximately four months. In recent years, there has been an increase in interest in treating cancer with natural products, including biotoxins. Biotoxins are biological resources, synthesized and secreted in the venom gland of different animals, containing several pharmacologically active compounds that may have great therapeutic value. The literature indicated that Melittin has multiple biological effects, such as antibacterial, antifungal, antiviral and antiparasitic. cytotoxic effects on various human tumor cell lines. The objective of this work is to evaluate the therapeutic efficacy of Melittin, in order to evaluate the antitumor and tumor stem cell inhibition potential, of this compound alone or in association with Doxorubicin, in canine, murine and human osteosarcoma cells in vitro regarding cell viability, cell migration and identifying death by necrosis or apoptosis.