Use of Secondary Metabolites Derived from Aspergillus Species as Anticancer Agents and Related Histological and Genetic Alterations: In Vitro Study

Abstract

The present work aimed to use natural derived fungal secondary metabolites as anticancer agents concerning cytotoxicity, apoptotic, genetic and histopathological profile. It was noticed that Asp. Terrius (Asp. T), Flavous (Asp. Fl) and Fumegatgus (Asp. Fu) induced variable toxic potential that was cell type, secondary metabolite type and concentration dependent. CaCo-2 cells showed less sensitivity than HuH-7 and in turn the IC50 was variable. Also, the apoptotic potential of Asp. species derived fungal secondary metabolites was proven via detection of up regulated pro apoptotic genes and down regulation of anti-apoptotic genes. The expression rate was cell type dependent. Concurrently apoptotic profile was accompanied with cellular DNA accumulation at the G2/M phase, an insignificant accumulation during the G0/G1 phase but there was not during the Pre-G1 and S phases. Also, there were a characteristic apoptotic features of treated cells presented as abnormal intra-nuclear eosinophyllic structures, necrotic cells with mixed euchromatin and heterochromatin, ruptured cell membranes, intranuclear eosinophyllic structures, apoptotic cells with irregular cellular and nuclear membranes, peripheral chromatin condensation and necrotic swollen cells with mixed euchromatin and heterochromatin. It can be concluded that A. secondary metabolites are promising agents can be used as a supplementary agents to current cancer drugs regimen applied.