Shailasree S
University of Mysore, India
Title: Response of cancer cell lines to small molecules (cytotoxicant) – Resulting in apoptosis and autophagy
Biography
Biography: Shailasree S
Abstract
Systematic screening of chemical libraries for small molecules revealed limited studies involving promising small molecules (lacking details on studies inferring drug-target interactions) with a capacity to kill cancer cells in-vitro. In the present study, myricetin was evaluated for its capacity to induce cytotoxic effect to neuroblastoma N2a cell and have listed the multi-target paradigm leading to its growth inhibition, apoptosis/autophagy. Toxic pathway, especially the upstream network of responses happening in toxicant-treated cancer cells prior to their programmed cell death is reported to provide an unbiased approach in unraveling changes deciding on the final fate of the cell. Studies preceding cell death by probe sets strongly pointed to changes in cluster related to genes with a role in chromosomal stability, eg., heterogeneous nuclear ribonucleoprotein (HNRNPM), that was down regulated. Those involved in adaptive carbon metabolism eg., argininosuccinate synthase (ASS1) were upregulated identified as intermediate response upon exposure to toxicant. Consumption of phosphocreatine and a parallel accumulation of creatine indicated exhaustion of cellular energy buffer. The prominent role of GSH to counter increasing cell stress as early adaptation before breakdown of cellular homeostatis was observed. Direct data substantiating cell death by apoptosis with p38 MAP kinase mediated p53 activated upregulation of caspase 3 is reported and will be discussed. Our data report on autophagy, representing an additional mechanism inducing cell death detected by accumulation of LC3-II protein and acridine-orange stained autophagosomes is included.