Apatone® induces autoschizic cell death in human bladder cancer cells

3^rd World Congress on Cancer Science & Therapy

October 21-23, 2013 DoubleTree by Hilton Hotel San Francisco Airport, CA, USA

Karen McGuire

ScientificTracks: J Cancer Sci Ther

Abstract :

Human bladder cancer cell lines RT4 and T24 were treated with Apatone®, a combination of vitamin C (VC) and vitamin K 3 in a 100:1 ratio, or VC or VK 3 alone. An MTT assay compared a 1 hr pulsed versus a 5 day continuous exposure. VC:VK 3 was synergistic, increasing the antitumor activity 12- to 24 fold for RT-4 cells and 6- to 41-fold for the T24 cells. Further study using flow cytometry revealed a growth arrested population and a population undergoing cell death. Growth arrested cells were blocked near the G 0 /G 1 - S-phase interface, while cell death was due to autoschizis. VC:VK 3 pulsed versus continuous exposure produced comparable CD 50 values, indicating a triggered response involving a catalase reversible redox mechanism generating hydrogen peroxide and other reactive oxygen species (ROS). ROS production caused lipid peroxidation and depletion of cellular thiols. When ATP levels were measured over 5 hrs to determine metabolic effects, a transient increase in ATP production was seen for VC and decreased ATP levels were seen following VK 3 treatment. VC:VK 3 , caused a unique spike in ATP levels after which ATP levels fell slowly. Further microscopic evaluation using live cell imaging with JC-1 revealed VC:VK 3 induced a loss in mitochondrial membrane potential. Though the exact cause of the ATP spike is unknown a possible mechanism is a shunt formed around a defective region of complex III of the electron transport chain from coenzyme Q to cytochrome c, producing a shift from glycolytic to oxidative metabolism and a dimunition of lactic acidosis.

Biography :

Karen McGuire is a biomedical engineer with a doctoral degree in cellular and molecular biology. She has worked in the area of drug development and cancer biology for the past 8 years testing a range of anti-cancer drugs to evaluate their synergistic activity and toxicity profiles both in vitro and in vivo . She has multiple peer reviewed publications and patent applications. She is the current president elect of the microscopy society of northeast Ohio, with experience in a range of imaging techniques including high content imaging for drug screening. She is also a member of the AACR and NAPW.