Abstract
BackgroundCancer is an international health problem, and the search for effective treatments is still in progress. Peptide therapy is focused on the development of short peptides with strong tumoricidal activity and low toxicity. In this study, we investigated the efficacy of a myxoma virus peptide analogue (RRM-MV) as a candidate for skin cancer therapy. RRM-MV was designed using the Resonant Recognition Model (RRM) and its effect was examined on human skin cancer and normal human skin cells in vitro.MethodsCell cultures were treated with various concentrations of the peptides at different incubation intervals. Cellular morphological changes (apoptosis and necrosis) were evaluated using confocal laser scanning microscopy. The cytotoxic effects of RRM-MV on human skin cancer and normal human skin cells were quantitatively determined by cytotoxicity and cell viability assays. The effect on human erythrocytes was also determined using quantitative hemolysis assay. DNA fragmentation assay was performed to detect early apoptotic events in treated cancer cells. Furthermore, to investigate the possible cell signalling pathway targeted by the peptides treatment, the levels of p-Akt expression in skin cancer and normal cells were detected by immunoblotting.ResultsOur results indicate that RRM-MV has a dose-dependent toxic effect on cancer cells only up to 18 h. The immunoblotting results indicated that the RRM-MV slightly increased p-Akt expression in melanoma and carcinoma cells, but did not seem to affect p-Akt expression in normal skin cells.ConclusionsRRM-MV targets and lethally harms cancer cells and leaves normal cells unharmed. It is able to reduce the cancer cell viability, disrupting the LDH activity in cancer cells and can significantly affect cancer progression. Further investigation into other cell signalling pathways is needed in the process leading to the in vivo testing of this peptide to prove its safety as a possible effective treatment for skin cancer.
Highlights
Cancer is an international health problem, and the search for effective treatments is still in progress
Detection of cellular apoptosis and necrosis The cytotoxic effects of Resonant Recognition Model (RRM)-Myxoma virus (MV) and RRM-C were detected on the human cancer cell lines (MM96L and Human squamous cell carcinoma cell line (COLO-16)) at different concentrations and different incubation times using confocal laser scanning microscopy (CLSM)
We found that RRM-MV induced apoptotic/necrotic effects in dose- and time-dependent manners in Human malignant melanoma cell line (MM96L) melanoma and COLO-16 carcinoma cell lines
Summary
Cancer is an international health problem, and the search for effective treatments is still in progress. These include oncolytic virotherapy, in which certain viruses selectively infect and kill cancerous cells, leaving normal cells unharmed in vitro [3,4,5,6] and in xenografted mice in vivo [7,8,9]. The mechanism of how MV selects and targets malignant cells is believed to be related to a unique tropism associated with the dysregulated intracellular signalling pathways, found in the majority of human cancers such as the Akt pathway [3]. It has been reported that Akt needs to be activated via interaction with a viral ankyrin-repeat host range factor before MV can infect human cancer cells [17]
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