A small cytotoxic peptide from frog elicits potent antitumor immunity to prevent local tumor growth and metastases

Aim: Anticancer immunochemotherapy represents an attractive paradigm to improve therapeutic responses and reduce side effects. Results & methodology: Here, we show that a naturally occurring host defense peptide, HN-1 inhibited multiple malignant cells proliferation and tumor growth in a xenografted human breast tumor model. Acting through MAPK/NF-κB pathways, HN-1 induced a caspase-independent mitochondrial apoptosis, as indicated by a p53-dependent increase of Bax/Bcl-2 ratio and the nuclear translocation of apoptosis inducing factor. Besides, HN-1 augmented CD4+/CD8+ T cells in 4T1 mammary carcinoma model, by enhancing the serum levels of cancer immunity-associated effectors. Meanwhile, HN-1 decreased the angiogenesis and infiltration of the tumor-associated macrophages. Conclusion: HN-1 induces caspase-independent cancer cells apoptosis and boosts cancer-resolving immunity without inducing potentially harmful pro-inflammatory responses.

Tumor Immune Response in the Presence of a Cytotoxic Peptide

We evaluated, by the flow cytometry technique, the viability of two tumor cell lines: colorectal carcinoma (HT-29) and human A549 arcinoma incubated with the cytotoxic peptide LL-37. The results obtained for the two cell lines HT-29 and A549 are significantly different under the action of cathelicidin LL-37. At high concentrations of 20mM, cellular apoptosis was over 30% higher for colorectal adenocarcinoma line compared to that by peptide exposure. Apoptosis was also significant in low-concentration (4uM) catechidine-labeled lung cancer cells for 48 h. Also, optimization of primers was sought to evaluate gene expression for, Bcl2, IL6, IL8. Determination of gene expression for these molecular targets under the action of the cytotoxic peptide was performed in order to evaluate the immune response of tumor cells. For this purpose, the genetic material (RNA) was extracted from cell cultures and reversed in cDNA, which was subsequently amplified by the qRT-PCR technique. Evaluation of tumor cell metabolism was done by determining the gene expression for Bcl2, IL6, IL8 by the action of the cytotoxic peptides used. The cytotoxic effect of cathelicidin LL-37 for the two cell lines HT29 and A549 is supported by the decrease in IL-6 and IL-8 gene expression. The increase in Bcl2 expression for cells exposed to the action of the peptide is explained by the increase in anti-apoptotic protein synthesis that explains the fight of tumor cells for survival and proliferation.

Enzyme-sensitive cytotoxic peptide–dendrimer conjugates enhance cell apoptosis and deep tumor penetration

Cytotoxic peptide conjugated PAMAM dendrimers with MMP2-sensitive PEG for efficient tumor penetration, cellular internalization and mitochondria disruption.