Role of oxidative stress in cytotoxicity of grape seed extract in human bladder cancer cells.

Abstract

In present study, we evaluated grape seed extract (GSE) efficacy against bladder cancer and associated mechanism in two different bladder cancer cell lines T24 and HTB9. A significant inhibitory effect of GSE on cancer cell viability was observed, which was due to apoptotic cell death. Cell death events were preceded by vacuolar appearance in cytoplasm, which under electron microscopy was confirmed as swollen mitochondrial organelle and autophagosomes. Through detailed in vitro studies, we established that GSE generated oxidative stress that initiated an apoptotic response as indicated by the reversal of GSE-mediated apoptosis when the cells were pre-treated with antioxidants prior to GSE. However, parallel to a strong apoptotic cell death event, GSE also caused a pro-survival autophagic event as evidenced by tracking the dynamics of LC3-II within the cells. Since the pro-death apoptotic response was stronger than the pro-survival autophagy induction within the cells, cell eventually succumbed to cellular death after GSE exposure. Together, the findings in the present study are both novel and highly significant in establishing, for the first time, that GSE-mediated oxidative stress causes a strong programmed cell death in human bladder cancer cells, suggesting and advocating the effectiveness of this non-toxic agent against this deadly malignancy.

• Authors: Komal Raina, Alpna Tyagi, Dileep Kumar, Rajesh Agarwal, Chapla Agarwal
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 61 Pg. 187-95 (Nov 2013) ISSN: 1873-6351 [Electronic] England
• PMID: 23831192 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Grape Seed Extract
• MAP1LC3A protein, human
• Microtubule-Associated Proteins
• Reactive Oxygen Species
• Superoxides

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Death (drug effects)
• Cell Line, Tumor (drug effects)
• Cytoplasm (drug effects)
• Grape Seed Extract (pharmacology)
• Humans
• Microtubule-Associated Proteins (metabolism)
• Oxidative Stress (drug effects, physiology)
• Reactive Oxygen Species (metabolism)
• Superoxides (metabolism)
• Urinary Bladder Neoplasms (drug therapy, metabolism, pathology)