Genetic and Histopathological Alterations in Caco-2 and HuH-7 Cells Treated with Secondary Metabolites of Marine fungi

Abstract

The present work aimed to study the activity of naturally derived fungal secondary metabolites as anticancer agents concerning their cytotoxicity, apoptotic, genetic, and histopathological profile. It was noticed that Aspergillus terreus, Aspergillus flavus, and Aspergillus fumigatus induced variable toxic potential that was cell type, secondary metabolite type, and concentration dependent. Human colonic adenocarcinoma cells (Caco-2) showed less sensitivity than hepatocyte-derived cellular carcinoma cells (HuH-7), and in turn, the half-maximal inhibitory concentration (IC₅₀) was variable. Also, the apoptotic potential of Aspergillus species-derived fungal secondary metabolites was proven via detection of up-regulated pro-apoptotic genes and down-regulation of anti-apoptotic genes. The expression level was cell type dependent. Concurrently, apoptotic profile was accompanied with cellular DNA accumulation at the G2/M phase, as well as an elevation in Pre-G1 phase but not during G0/G1 and S phases. Also, there were characteristic apoptotic features of treated cells presented as abnormal intra-nuclear eosinophilic structures, dead cells with mixed euchromatin and heterochromatin, ruptured cell membranes, apoptotic cells with irregular cellular and nuclear membranes, as well as peripheral chromatin condensation. It can be concluded that Aspergillus secondary metabolites are promising agents that can be used as supplementary agents to the currently applied anti-cancer drug regimen.

Keywords: Apoptosis; Aspergillus spp.; Cytotoxicity; Flow cytometry; Histopathology.