ABSTRACT
Cervical cancer (CC) is classified as the fourth most common type of cancer in women worldwide and remains a serious public health problem in many underdeveloped countries. Human papillomavirus (HPV), mainly types 16 and 18, has been established as a precursory etiologic agent for this type of cancer. Several therapeutic attempts have been studied and applied, aiming at its control. However, not only do classical treatments such as chemotherapies and radiotherapies target tumor cells, but also they cause damage to several healthy cells. For these reasons, the search for new biologically active chemotherapeutic components is of great importance. In this study, we investigated the effect of Tityus serrulatus scorpion venom (TsV) on CC lines. There are very few studies exploring venom of scorpions, and, to our knowledge, no study has been conducted using the venom of the scorpion TsV for treatment of cervical cancer lines. After challenge with TsV, the MTT assay demonstrated cytotoxic effect on HeLa line. Similarly, the cell death process in HeLa analyzed by flow cytometry suggests death via caspase, since the pan-caspase inhibitor z-VAD-fmk significantly reduced the apoptotic response to the treatment. These results suggest that venom of TsV can be a potential source for the isolation of effective antiproliferative and apoptotic molecules in the treatment of CC.
ABSTRACT
Cervical cancer (CC) is classified as the fourth most common type of cancer in women worldwide and remains a serious public health problem in many underdeveloped countries. Human papillomavirus (HPV), mainly types 16 and 18, has been established as a precursory etiologic agent for this type of cancer. Several therapeutic attempts have been studied and applied, aiming at its control. However, not only do classical treatments such as chemotherapies and radiotherapies target tumor cells, but also they cause damage to several healthy cells. For these reasons, the search for new biologically active chemotherapeutic components is of great importance. In this study, we investigated the effect of Tityus serrulatus scorpion venom (TsV) on CC lines. There are very few studies exploring venom of scorpions, and, to our knowledge, no study has been conducted using the venom of the scorpion TsV for treatment of cervical cancer lines. After challenge with TsV, the MTT assay demonstrated cytotoxic effect on HeLa line. Similarly, the cell death process in HeLa analyzed by flow cytometry suggests death via caspase, since the pan-caspase inhibitor z-VAD-fmk significantly reduced the apoptotic response to the treatment. These results suggest that venom of TsV can be a potential source for the isolation of effective antiproliferative and apoptotic molecules in the treatment of CC.
ABSTRACT
Snakebite envenoming is a tropical disease neglected worldwide. In Brazil, the Crotalus durissus cascavella (CDC) snake belongs to a genus with venom of highest lethality. A search for new immunoadjuvants aimed to expand the therapeutic alternatives to improve vaccines and antivenom. This approach proposed to produce small and narrow-sized cationic CDC venom-loaded chitosan nanoparticles (CHNP) able to induce antibody response against the CDC venom. The ionic gelation method induced the formation of stable and slightly smooth spherical nanoparticles (<160?nm) with protein loading efficiency superior to 90%. The interactions between venom proteins and CHNP assessed using FT-IR spectroscopy corroborated with the in vitro release behavior of proteins from nanoparticles. Finally, the immunization animal model using BALB/c mice demonstrated the higher effectiveness of CDC venom-loaded CHNP compared to aluminum hydroxide, a conventional immunoadjuvant. Thus, CHNPs loaded with CDC venom exhibited a promising biotechnological approach to immunotherapy.
ABSTRACT
Snakebite envenoming is a tropical disease neglected worldwide. In Brazil, the Crotalus durissus cascavella (CDC) snake belongs to a genus with venom of highest lethality. A search for new immunoadjuvants aimed to expand the therapeutic alternatives to improve vaccines and antivenom. This approach proposed to produce small and narrow-sized cationic CDC venom-loaded chitosan nanoparticles (CHNP) able to induce antibody response against the CDC venom. The ionic gelation method induced the formation of stable and slightly smooth spherical nanoparticles (<160?nm) with protein loading efficiency superior to 90%. The interactions between venom proteins and CHNP assessed using FT-IR spectroscopy corroborated with the in vitro release behavior of proteins from nanoparticles. Finally, the immunization animal model using BALB/c mice demonstrated the higher effectiveness of CDC venom-loaded CHNP compared to aluminum hydroxide, a conventional immunoadjuvant. Thus, CHNPs loaded with CDC venom exhibited a promising biotechnological approach to immunotherapy.
ABSTRACT
In Brazil, envenomation by snakes of the genus Bothrops is clinically relevant, particularly for the species Bothrops jararaca and B. erythromelas. The most effective treatment for envenomation by snakes is the administration of antivenoms associated with adjuvants. Novel adjuvants are required to reduce side effects and maximize the efficiency of conventional serum and vaccine formulations. The polymer chitosan has been shown to have immunoadjuvant properties, and it has been used as a platform for delivery systems. In this context, we evaluated the potential immunoadjuvant properties of chitosan nanoparticles (CNPs) loaded with B. jararaca and B. erythromelas venoms in the production of sera against these venoms. Stable CNPs were obtained by ionic gelation, and mice were immunized subcutaneously for 6 weeks with 100 mu L of each snake venom at concentrations of 5.0 or 10.0% (w/w), encapsulated in CNPs or associated with aluminium hydroxide (AH). The evaluation of protein interactions with the CNPs revealed their ability to induce antibody levels equivalent to those of AH, even with smaller doses of antigen. In addition, the CNPs were less inflammatory due to their modified release of proteins. CNPs provide a promising approach for peptide/protein delivery from snake venom and will be useful for new vaccines.
