Abstract
The main aim of the present work was to investigate the potential effect of acetone extract of Ficus religosa leaf (FAE) in multiple apoptosis signalling in human breast cancer cells. FAE treatment significantly induced dose and time dependent, irreversible inhibition of breast cancer cell growth with moderate toxicity to normal breast epithelial cells. This observation was validated using Sulforhodamine B assay. Cell cycle analysis by Flow cytometry showed cell cycle arrest in G1 phase and induction of sub-G0 peak. FAE induced chromatin condensation and displayed an increase in apoptotic population in Annexin V-FITC/PI (Fluorescein isothiocyanate/Propidium iodide) double staining. FAE stimulated the loss of mitochondrial membrane potential in multiple breast cancer cell lines when compared to normal diploid cells. To understand the role of Bax in FAE induced apoptosis, we employed a sensitive cell based platform of MCF-7 cells expressing Bax-EGFP. Bax translocation to mitochondria was accompanied by the disruption of mitochondrial membrane potential and marked elevation in LEHDase activity (Caspase 9). Consistent with this data, FAE induced Caspase activation as evidenced by ratio change in FRET Caspase sensor expressing MCF-7 cell line and cleavage of prominent Caspases and PARP. Interestingly, FAE accelerated cell death in a mitochondrial dependent manner in continuous live cell imaging mode indicating its possible photosensitizing effect. Intracellular generation of reactive oxygen species (ROS) by FAE played a critical role in mediating apoptotic cell death and photosensitizing activity. FAE induced dose and time dependent inhibition of cancer cell growth which was associated with Bax translocation and mitochondria mediated apoptosis with the activation of Caspase 9 dependent Caspase cascade. FAE also possessed strong photosensitizing effect on cancer cell line that was mediated through rapid mitochondrial transmembrane potential loss and partial Caspase activation involving generation of intracellular ROS.
Highlights
Herbal plants and plant-derived medicines have been widely used in traditional cultures all over the world and have gained popularity in modern society as natural alternatives to produce new potential therapeutic compounds for combating diseases [1]
The present study shows the effect of acetone extract of F.religiosa leaves on the dose and time dependent growth inhibition of multiple breast cancer cell lines which was associated with Bax translocation and mitochondria mediated apoptosis with the activation of Caspase 9 dependent pathway
The results suggested that Ficus religosa leaf (FAE) induced cell death in most breast cancer cells with loss of mitochondrial membrane potential and chromatin condensation
Summary
Herbal plants and plant-derived medicines have been widely used in traditional cultures all over the world and have gained popularity in modern society as natural alternatives to produce new potential therapeutic compounds for combating diseases [1]. Pharmacological studies carried out on the fresh plant materials of F.religiosa provide a pragmatic support for its numerous traditional uses. Singh et al [7] had suggested a detailed investigation for its potential against cancer, cardiovascular, neuro inflammatory, neuropsychiatric, oxidative stress related disorders and parasitic infections. Most of the pharmacological studies were aimed on validating its traditional uses for wound healing [8,9], anti-bacterial [10], anti-convulsant [11], anti-diabetic [12], anti-oxidant [13], anti-inflammatory [14], acetyl cholinesterase inhibitory activity [15] and anti-anxiety activity [16]. The methanolic extract of F.religiosa leaf exerts strong neuroprotective effect against inflammation caused by mediators such as nitric oxide and cytokines in LPS (Lipopolysaccharide)stimulated microglia via the MAPK (Mitogen Activated Protein Kinase) pathway [17]
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