Chaetomium sp. Extract Induced Cytotoxicity to MDA-MB-231 Human Breast Cancer Cells via Dysfunction of Mitochondria Inducing Apoptosis.

Premna serratifolia Linn, a medicinally prominent plant is widely used in Ayruvedic, Siddha and Homeopathy medicinal treatments. In this study, out of its leaf fungal endophytes, about 68 Chaetomium sp. exhibited highest percentage similarity to the nearest genera (98.6 %) and thus were evaluated for its therapeutic properties. Chaetomium ethyl acetate extract contained flavonoids and phenolic compounds exhibited promising antioxidant activity against the 2,2-diphenyl-1-picrylhydrazyl radical. Chaetomium ethyl acetate extract induced cytotoxicity to MDA-MB-231, human breast cancer cells. Maximum cytotoxic activity and cell death was obtained with half maximal effective concentration of 96.82±5.23 µg upon exposure for 48 h. Apoptosis with chromatin condensation was visualized with acridine orange and propidium iodide dual staining at these conditions. It could stimulate cancerous MDA-MB-231 cells to undergo apoptosis (60.24 %) as evidenced by flow cytometer analysis mediated through elevated levels of reactive oxygen species (7.5 folds). Such excess reactive oxygen species generation resulted structural injury of the mitochondrial membrane its dissipation of membrane potential as identified by shift from red to green fluorescence of 5,5,6,6'-tetrachloro-1,1',3,3' tetraethylbenzimi-dazoylcarbocyanine iodide dye. One of the bioactive bestowing therapeutic potential was identified as chrysin, a flavone, by high performance liquid chromatography analysis of the extract against the standard chrysin (Rt, 24.68 min). Thus, an effective MDA-MB-231 apoptotic event by the extract is reported. [ABSTRACT FROM AUTHOR]