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Abstract

Antimicrobial peptides (AMPs) are a new source of potential anticancer drugs. One such AMP is the shrimp antilipopolysaccharide factor (SALF), an AMP isolated from Penaeus monodon; the SALF was previously reported to induce tumor cell death. However, the mechanism by which the SALF regulates these pathways remains unclear. In this study, we identified that the SALF modulates mitochondria- and caspase-dependent apoptotic pathways in human cervical cancer cells. The SALF was found to inhibit the growth of four cervical cancer cell lines: HeLa, HeLa 299, C33A, and Ca ski. In addition, a fluorescence-activated cell sorting (FACS) analysis revealed that the SALF induced death and G2/M phase arrest in HeLa and HeLa 299 cells. The SALF itself was found to be localized to the cytosol and nuclei of HeLa cells by confocal imaging. Staining with acridine orange/ ethidium bromide and analysis of DNA fragmentation confirmed that the SALF induced apoptosis in HeLa cells. Moreover, caspases-3 and -9 were found to be involved in SALF-induced apoptosis, through the use of various caspase inhibitors in vitro and immunohistochemistry in vivo. Finally, the SALF was found to induce depolarization of mitochondrial membranes with associated translocation of the AIF to nuclei, and to affect levels of Bcl-2 family proteins in HeLa cells. Taken together, our findings indicate that the SALF induces mitochondria- and caspase-dependent apoptotic pathways in HeLa cells. We suggest that the SALF may be an effective treatment for cervical cancer, either alone or in combination with traditional therapies.

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