Abstract
Shrimp anti-lipopolysaccharide factor (SALF) is an antimicrobial peptide with reported anticancer activities, such as suppression of tumor progression. In this study, we prepared a potential cancer vaccine comprised of SALF in conjunction with the cell lysate of inactivated murine bladder carcinoma cells (MBT-2), and evaluated its efficacy in a mouse tumor model. Our study shows that SALF added to cell culture media inhibits growth progression of MBT-2, and that SALF together with inactivated MBT-2 lysate elevates the level of inflammasome activity, and modulates the levels of IL-1β, MCP-1, IL-6, IL-12, and TNF-α in mouse macrophages. Immunization of 7, 14, and 21 day-old mice with the vaccine prevented growth of MBT-2 cell-mediated tumors. The vaccine was found to enhance expression of T-cell, cytotoxic T cells, and NK cells in the immunized mice groups. Recruitment of macrophages, T-helper cells, and NK cells was enhanced, but levels of VEGF were decreased in immunized mice. This report provides empirical evidence that our SALF as vaccine adjuvant enhances antitumor immunity in mice.
Highlights
Antimicrobial peptides (AMPs) play an important role as first-line defensins, warding off the invasion of pathogens [1]
In order to establish whether Shrimp anti-lipopolysaccharide factor (SALF) is effective against bladder tumors, we examined the proliferation of Murine Bladder Tumor (MBT)-2 cells treated with 0, 10, 20, or 40 μg/mL of SALF for 24 h (Figure 1A)
We examined the level of IL-1β in J774A.1 cells treated with non-toxic SALF concentrations and inactivated MBT-2 lysate (Figure 2A)
Summary
Antimicrobial peptides (AMPs) play an important role as first-line defensins, warding off the invasion of pathogens [1]. One such AMP, shrimp anti-lipopolysaccharide factor (SALF), was identified from the hemocytes of the shrimp Penaeus monodon [2,3]. SALF possesses a broad spectrum of anti-microbial activities, effective against filamentous fungi and Gram-positive/-negative bacteria [4,5]. SALF induces cell apoptosis (through the death receptor in tumor cells), activates caspases-6, -7, and -9, and down regulates bcl-2 and nuclear factor (NF)-κB [10]. In addition to its in vitro anti-tumorigenic activities, SALF has an intrinsic ability to diminish tumor xenografts in mouse models
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