ABSTRACT
The highest production of withaferin A and withanone was achieved when sucrose and sucrose+glucose were used individually as carbon sources. Fifteen gene-targets were identified and were investigated for their role in a specific cancer cell killing activity of i-Extract and withaferin A and withanone by undertaking the shRNA-mediated gene silencing approach. The Molecular Dynamics simulation results suggesting the thermodynamic and structural stability of TPX2-Aurora A in complex with withanone further substantiates the binding. Withanone and withaferin A in the i-Extract retained the selective cancer cell killing activity and found that it also has significant antimigratory, -invasive, and -angiogenic activities, in both in vitro and in vivo assays. Withanone protects cells from methoxyacetic acid-induced toxicity by suppressing the reactive oxygen species levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings suggest further studies of withanone as an adjuvant in consumer products where ester phthalates are cause of health concern.
