With the emergence of many antibiotic-resistant strains worldwide, antimicrobial peptides (AMPs) are being evaluated as promising alternatives to conventional antibiotics. P3, a novel hemoglobin peptide derived from bovine erythrocytes, exhibited modest antimicrobial activity in vitro. We evaluated the antimicrobial activities of P3 and an analog, JH-3, both in vitro and in vivo. The MICs of P3 and JH-3 ranged from 3.125 g/ml to 50 g/ml when a wide spectrum of bacteria was tested, including multidrug-resistant strains. P3 killed bacteria within 30 min by disrupting the bacterial cytoplasmic membrane and disturbing the intracellular calcium balance. Circular dichroism (CD) spectrometry showed that P3 assumed an ␣-helical conformation in bacterial lipid membranes, which was indispensable for antimicrobial activity. Importantly, the 50% lethal dose (LD 50 ) of JH-3 was 180 mg/kg of mouse body weight after intraperitoneal (i.p.) injection, and no death was observed at any dose up to 240 mg/kg body weight following subcutaneous (s.c.) injection. Furthermore, JH-3 significantly decreased the bacterial count and rescued infected mice in a model of mouse bacteremia. In conclusion, P3 and an analog exhibited potent antimicrobial activities and relatively low toxicities in a mouse model, indicating that they may be useful for treating infections caused by drug-resistant bacteria.T he overuse of traditional antibiotics has triggered the frequent emergence of multidrug-resistant (MDR) bacteria, which pose significant threats to public health. Bacterial resistance is usually attributable to mutations and can spread, rendering the problem worse (1-3). Extensively mutated bacteria become resistant to many conventional chemotherapeutics. Since the early 1960s, many novel antibiotics have been prepared, but these are usually chemical variations of older and conventional antibiotics (4). There is an urgent need to find novel antimicrobial agents that control infections caused by MDR bacteria.Antimicrobial peptides (AMPs) have recently attracted significant attention (5). They are primitive components of innate immune systems and play multiple roles in immune defense (6, 7). AMPs are widespread in unicellular organisms, plants, and animals, and more than 1,600 have been identified in a wide range of organisms (8-10). Most natural AMPs exhibit broad-spectrum activities against bacteria (including MDR bacteria), fungi, viruses (including HIV), and tumors (11-13). Although many potent AMPs have been identified, a lack of knowledge about the mechanisms of action and high-level AMP toxicities are major obstacles on the path to clinical use (14). Therefore, the design of novel potent AMPs exhibiting low toxicities in vivo and the identification of the mechanisms of AMP-membrane interactions are important for the development of novel antimicrobial agents.Recently, we reported the first isolation of P3, a component of the bovine hemoglobin ␣-subunit (15). Its primary sequence is VNFKLLSHSLLVTLASHL (1,992.401 Da). The bovine hemoglobin P3 ...

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In this study, a novel 18-residue linear antimicrobial peptide derived from the central part of the bovine hemoglobin a-subunit was identified. The peptide was purified by a combination of cationic exchange and reversedphase high-performance liquid chromatography. The sequence was determined to be VNFKLLSHSLLVTLASHL. The theoretical molecular weight of this peptide was calculated to be 1992.38 Da, which is the same as that determined (1992.401 Da) by matrix-assisted laser desorption ionization mass spectrometry. Sequence analysis showed that there is a high degree of homology in this peptide among hemoglobin asubunits of bovine, sheep, deer, porcine, and human. In a radial-diffusion plate assay, this purified peptide exhibited antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans.

Traditional Chinese medicines have been recognized as especially promising anticancer agents in modern anticancer research. Halofuginone (HF), an analog of quinazolinone alkaloid extracted from Dichroa febrifuga, is widely used in traditional medicine. However, whether HF inhibits the growth of breast cancer cells and/or reduces the migration and invasion of MCF-7 human breast cancer cells, as well as the underlying mechanisms in vitro, remains unclear. In this study, we report that an HF extract inhibits the growth of MCF-7 cells and reduces their migration and invasion, an important feature of potential anticancer agents. In addition, HF significantly increases the activation of autophagy, which is closely associated with tumor metastasis. As STMN1 and p53 have been closely implicated in breast cancer progression, we analyzed their expression in the context of HF extract treatment. Western blot analysis showed that HF suppresses STMN1 and p53 expression and activity in an autophagy-dependent manner. Collectively, these data indicate that activation of autophagy reduces expression of STMN1 and p53, and the migration and invasion of cancer cells contributes to the anti-cancer effects of the HF. These findings may provide new insight into breast cancer prevention and therapy.

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