ABSTRACT
BACKGROUND: Antimicrobial peptides, an extract from nature, are a basic component of host immunity that make toxic effect on highly proliferative cells. They have attracted extensive attention of scientists. The understanding of the antineoplastic mechanism of antimicrobial peptides can contribute to its application in clinical practice. OBJECTIVE: To summarize the research advances in antineoplastic mechanism of antimicrobial peptides. METHODS: The first author conducted a computer-based retrieval of PubMed, Springerlink, Web of Science, and ScienceDirect databases for relevant articles published from January 2015 to May 2019. The keywords were “antimicrobial, peptide, antitumor mechanisms, antitumor activity and anti-neoplastic”. The articles concerning antineoplastic mechanism of antimicrobial peptides and research progress were selected. RESULTS AND CONCLUSION: Cationic antimicrobial peptides synthesized by ribosomes and the host defense peptides can interact with the membrane of bacteria, which showed a broad-spectrum antimicrobial activity. Compared with normal cells, the proportion of phosphatidylserine on the surface of cancer cells, which is negatively charged, is increased dramatically. As a result, the cationic amphiphilic peptides are good candidate for the antineoplastic drugs, and possess a high selectivity. There are two major antitumor mechanism of antimicrobial peptides, which are selective membrane destruction and non-membrane dissolution (α-defensin-1 and lactoferrin B). The clinical application of antimicrobial peptides against tumors is mainly restricted by their stability and the ways to administration. By optimizing its structure and drug delivery systems, these antimicrobial peptides will play a critical role in the cancer treatment.
ABSTRACT
To analyze the protein composition of Brucea javanica seeds and evaluate the cytotoxicity of its gulbulin hydrolysates. Four protein fractions of albumin, gulbulin, prolamin and glutelin were sequentially extracted and then quantified by Kjeldahl method. Different kinds of proteases were applied to hydrolyze B.javanica gulbulin, and MTT assay was used to evaluate the cytotoxicity of low molecular weight hydrolysates (≤3 kDa) on human breast cancer MCF-7 cell. The results showed that： the total protein content of B.javanica seeds was 17.47%, albumin, gulbulin, coxin, glutelin and residue protein accounted for 15.01%, 8.11%, 2.47%, 44.92% and 23.62% of the total protein content, respectively. The hydrolysates (≤3 kDa) of B.javanica globulin produced by pepsin showed significant growth inhibitory activity on MCF-7 cells, and the IC₅₀ value was（6.52±0.01） mg•L⁻¹ after 72 h of incubation. Protein was abundant in B.javanica seeds, and its peptides demonstrated specific cytotoxicity on MCF-7 cell line in vitro, suggesting antitumor active ingredient can be further generated from B.javanica seeds.
ABSTRACT
The generation and activity of serum neuralizing antibody in cynomolgus monkeys and SD rats undergoing long-term toxicity study with antitumor peptides HM-3 were investigated.The rats were administered intravenously with HM-3 at doses of 4.5 mg/kg,13.5 mg/kg,and 40.5 mg/kg for 6 months,and the cynomolgus monkeys were administrated intravenously with HM-3 at doses of 3 mg/kg,9 mg/kg and 27 mg/kg for 6 months,respectively.Anti-HM-3 antibodies and their neutralizing activities in serum samples taken every month after the administrations were determined by ELISA and cell migration assay,respectively.During the long-term administrations,anti-HM-3 antibodies were generated in some SD rats at high and moderate dose groups,and the antibody-neutralizing activities could be detected in a number of these samples (P ＜0.05).However,activity could be detected in very few monkeys (P ＜ 0.05),and the antibody titers were not correlated with the neutralizing activities.Therefore,we conclude that the antigenicity of HM-3 was low,but after long-term administration at high dose,low affinity neutralizing antibody could be generated in small number of samples.