Anticancer potential of human intestinal defensin 5 against 1, 2-dimethylhydrazine dihydrochloride induced colon cancer: A therapeutic approach

Abstract

The escalating predicament of multidrug resistant cancer cells and associated side effects of conventional chemotherapy necessitates the exploration of alternative anticancer therapies. The present study evaluated anticancer therapeutic potential of human defensin 5 (HD-5) against colon cancer. The in vivo anticancer efficacy of HD-5 against 1,2-dimethylhydrazine (DMH) induced colon cancer was elucidated in terms of tumor biostatistics, number of aberrant crypt foci (ACF), in situ apoptosis assay,changes in morphological as well as histological architecture of colon(s). The direct interaction of peptide was investigated by incubating peptide with normal and/or cancerous colonocytes followed by phase contrast, Hoechst 3342 and AO/PI staining as well as confocal microscopy. Changes in membrane dynamics were evaluated by MC 540 and N-NBD-PE staining. In vivo decrease(s) in tumor parameters, number of aberrant crypt foci along with marked increase in the rate of apoptosis was observed.H&E staining revealed neutrophils infiltration and restoration of normal architecture in treated colon(s) which was consistent with scanning electron microscopic observations. Furthermore, non-membranolytic mechanism was found to be acquired by peptide as it could traverse cell membrane gaining access to nucleus and cytoplasm thereby disintegrating cellular architecture. MC 540 and NBD-PE staining revealed that peptide could bind to cancerous cells by taking advantage of altered fluidity levels. Our results indicated that HD-5 exhibited strong cancer cell killing and does not affect normal host cells. The peptide can be exploited as promising option to combat developing menace of colon cancer and/or can at least be used as an adjunct to present day chemotherapies.