Icariin zeinmersomes display enhanced anti-proliferative and pro-apoptotic activities in colon cancer cells

Abstract

Background

The present study aimed at investigating the effectiveness of zeinmersomes (ZMS)-based nano-formulation to enhance icariin (ICA) cytotoxicity in colon cancer cells. The prepared ICA-ZMS was characterized with respect to particle size, entrapment efficiency, and in vitro release.

Results

ICA-ZMS showed higher cytotoxicity in HCT-116 cells compared to HT-29 and Caco-2 cells with almost no cytotoxicity in normal HCoEpC colon cells. In this regard, ICA-ZMS exhibited potentiated cytotoxicity as compared to ICA-raw. In HCT-116 cells, ICA loaded on ZMS exhibited better cellular penetration compared to ICA-raw. The accumulation of HCT-116 in the S phase was identified using cell cycle analysis. Annexin V staining highlighted a potent pro-apoptotic activity of the prepared ICA-ZMS. This with confirmed by the observed up-regulated Bax and down-regulated Bcl-2 mRNA expression. Further, mRNA expression of p53, cytochrome C, and caspase-3 was significantly increased by exposing cells to ICA-ZMS. This was associated with a detectable decline in mitochondrial membrane potential. These data were confirmed by the ability of ICA-ZMS to significantly enhance the life span of Ehrlich ascites carcinoma-bearing mice.

Conclusion

This study suggests that the loading of ICA on ZMS nanoparticles enhances its cytotoxic and pro-apoptotic activities. This involves modulation of p53-dependent mitochondrial signaling.