Antitumor effect of algae silver nanoparticles on human triple negative breast cancer cells.

In recent years, metallic nanoparticles have gained increasing attention due to their prospective applications in the field of nanomedicine, with increasing research into their use in cancer therapy. In this current research, we investigated the effect of green synthesized Silver Nanoparticles (AgNPs) capped with Noctiluca scintillans algae extract. The phytochemicals present in the shell of AgNPs were identified using GC-MS. Different compounds with anticancer activity such as n-hexadecanoic acid, beta-sitosterol, stigmasterol and palmitic acid were detected among others. The effects of Algae-AgNPs synthesized were tested on MDA-MB-231 human breast cancer cells and HaCat human keratinocyte normal cells. Cell viability assay revealed a time and dose-dependent effect against breast cancer cells with a less potent effect against normal cells. The cell viability reduction is not attributed to a cytotoxic nor an antiproliferative effect of the Algae-AgNPs as attested by LDH release and BrdU incorporation. Algae-AgNPs exhibited an exceptional ability to specifically induce apoptosis in cancer cells and not normal cells. The observed effects are not attributed to the AgNPs, as demonstrated by the lack of impact of the Starch-AgNPs (used as a negative control) on cell survival and apoptosis. In addition to that, we show that Algae-AgNPs significantly reduced tumor cell migration by downregulation of matrix metalloprotease-9 levels. In vivo, the breast cancer xenograft model showed a significant reduction of tumor growth in mice treated with Algae-AgNPs. These findings highlight the promising potential of the green synthesized AgNPs as a safe targeted therapy for cancer treatment.

The 14-Kilodalton Human Growth Hormone Fragment a Potent Inhibitor of Angiogenesis and Tumor Metastasis.

The 14-kilodalton human growth hormone (14 kDa hGH) N-terminal fragment derived from the proteolytic cleavage of its full-length counterpart has been shown to sustain antiangiogenic potentials. This study investigated the antitumoral and antimetastatic effects of 14 kDa hGH on B16-F10 murine melanoma cells. B16-F10 murine melanoma cells transfected with 14 kDa hGH expression vectors showed a significant reduction in cellular proliferation and migration associated with an increase in cell apoptosis in vitro. In vivo, 14 kDa hGH mitigated tumor growth and metastasis of B16-F10 cells and was associated with a significant reduction in tumor angiogenesis. Similarly, 14 kDa hGH expression reduced human brain microvascular endothelial (HBME) cell proliferation, migration, and tube formation abilities and triggered apoptosis in vitro. The antiangiogenic effects of 14 kDa hGH on HBME cells were abolished when we stably downregulated plasminogen activator inhibitor-1 (PAI-1) expression in vitro. In this study, we showed the potential anticancer role of 14 kDa hGH, its ability to inhibit primary tumor growth and metastasis establishment, and the possible involvement of PAI-1 in promoting its antiangiogenic effects. Therefore, these results suggest that the 14 kDa hGH fragment can be used as a therapeutic molecule to inhibit angiogenesis and cancer progression.

The Plasminogen-Activator Plasmin System in Physiological and Pathophysiological Angiogenesis.

Angiogenesis is a process associated with the migration and proliferation of endothelial cells (EC) to form new blood vessels. It is involved in various physiological and pathophysiological conditions and is controlled by a wide range of proangiogenic and antiangiogenic molecules. The plasminogen activator-plasmin system plays a major role in the extracellular matrix remodeling process necessary for angiogenesis. Urokinase/tissue-type plasminogen activators (uPA/tPA) convert plasminogen into the active enzyme plasmin, which in turn activates matrix metalloproteinases and degrades the extracellular matrix releasing growth factors and proangiogenic molecules such as the vascular endothelial growth factor (VEGF-A). The plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of uPA and tPA, thereby an inhibitor of pericellular proteolysis and intravascular fibrinolysis, respectively. Paradoxically, PAI-1, which is expressed by EC during angiogenesis, is elevated in several cancers and is found to promote angiogenesis by regulating plasmin-mediated proteolysis and by promoting cellular migration through vitronectin. The urokinase-type plasminogen activator receptor (uPAR) also induces EC cellular migration during angiogenesis via interacting with signaling partners. Understanding the molecular functions of the plasminogen activator plasmin system and targeting angiogenesis via blocking serine proteases or their interactions with other molecules is one of the major therapeutic strategies scientists have been attracted to in controlling tumor growth and other pathological conditions characterized by neovascularization.