Abstract
Recently, we have found that the skin secretions of the Amazonian tree frog Phyllomedusa bicolor contains molecules with antitumor and angiostatic activities and identified one of them as the antimicrobial peptide dermaseptin (Drs) B2. In the present study we further explored the in vitro and in vivo antitumor activity of this molecule and investigated its mechanism of action. We showed that Drs B2 inhibits the proliferation and colony formation of various human tumor cell types, and the proliferation and capillary formation of endothelial cells in vitro. Furthermore, Drs B2 inhibited tumor growth of the human prostate adenocarcinoma cell line PC3 in a xenograft model in vivo. Research on the mechanism of action of Drs B2 on tumor PC3 cells demonstrated a rapid increasing amount of cytosolic lactate dehydrogenase, no activation of caspase-3, and no changes in mitochondrial membrane potential. Confocal microscopy analysis revealed that Drs B2 can interact with the tumor cell surface, aggregate and penetrate the cells. These data together indicate that Drs B2 does not act by apoptosis but possibly by necrosis. In conclusion, Drs B2 could be considered as an interesting and promising pharmacological and therapeutic leader molecule for the treatment of cancer.
Highlights
Cancer is a disease that nowadays seems to become the most important cause of death
Results are expressed in growth inhibition 50% (GI50) which indicates the peptide concentration that inhibit 50% of the cell growth
In this study we showed that Drs B2 displays a selective inhibition on the proliferation of all tested tumor adherent and non-adherent cell lines, with GI50 values in the low micromolar range
Summary
Cancer is a disease that nowadays seems to become the most important cause of death. Origin and state of the cancer several managing options exist, including surgery, radiation therapy, and chemotherapy. Concerning chemotherapy, the activity of most chemotherapeutic agents counteract against the healthy fast-dividing cells of the body, such as blood cells and the cells lining the mouth, stomach, and intestines. They can depress the immune system and cancer cells frequently develop resistance to many anti-cancer drugs that greatly reduces their therapeutic usefulness [1,2]. Other common side effects include fatigue, tendency to bleed gastrointestinal distress, rapid weight loss, or occasionally in weight gain, and temporary hair loss
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