Cytotoxic effect of p-coumaric acid on neuroblastoma, n2a cell via generation of reactive oxygen species leading to dysfunction of mitochondria inducing apoptosis and autophagy

Shailasree, S. and Venkataramana, M. and Niranjana, S. R. and Prakash, H. S. (2015) Cytotoxic effect of p-coumaric acid on neuroblastoma, n2a cell via generation of reactive oxygen species leading to dysfunction of mitochondria inducing apoptosis and autophagy. MOLECULAR NEUROBIOLOGY, 51 (1). pp. 119-130. ISSN 1559-1182

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Official URL: https://doi.org/10.1007/s12035-014-8700-2

Abstract

p-Coumaric acid (p-CA), an ubiquitous plant phenolic acid, has been proven to render protection against pathological conditions. In the present study, p-CA was evaluated for its capacity to induce cytotoxic effect to neuroblastoma N2a cells and we report here the possible mechanism of its action. p-CA at a concentration of 150 mu mol/L, upon exposure for 72 h, stimulated 81.23 % of cells to apoptosis, as evidenced by flow cytometer studies mediated through elevated levels of ROS (7.5-fold over control). Excess ROS production activated structural injury to mitochondrial membrane, observed as dissipation of its membrane potential and followed by the release of cytochrome c (8.73-fold). Enhanced generation of intracellular ROS correlated well with the decreased levels (similar to 60 %) of intracellular GSH. Sensitizing neuroblastoma cells for induction of apoptosis by p-CA identified p53-mediated upregulated accumulation of caspase-8 messenger RNA (2.8-fold). Our data report on autophagy, representing an additional mechanism of p-CA to induce growth arrest, detected by immunoblotting and fluorescence, correlated with accumulation of elevated levels (1.2-fold) of the LC3-II protein and acridine orange-stained autophagosomes, both autophagy markers. The present study indicates p-CA was effective in production of ROS-dependent mitochondrial damage-induced cytotoxicity in N2a cells.

Item Type: Article
Subjects: B Life Science > Biotechnology
Divisions: Department of > Biotechnology
Department of > Institution of Excellence
Depositing User: Shrirekha N
Date Deposited: 17 Jun 2019 04:49
Last Modified: 17 Jun 2019 04:49
URI: http://eprints.uni-mysore.ac.in/id/eprint/2794

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