TY - JOUR
T1 - Cell damage and death by autoschizis in human bladder (RT4) carcinoma cells resulting from treatment with ascorbate and menadione
AU - Gilloteaux, Jacques
AU - Jamison, James M.
AU - Neal, Deborah R.
AU - Loukas, Marios
AU - Doberzstyn, Theresa
AU - Summers, Jack L
PY - 2010
Y1 - 2010
N2 - A human bladder carcinoma cell line RT4 was sham-treated with buffer or treated with ascorbate (VC) alone, menadione alone (VK3), or a combination of ascorbate:menadione (VCVK3) for 1, 2, and 4h. Cytotoxic damage was found to be treatment-dependent in this sequence: VCVK3>VC>VK3>sham. The combined treatment induced the greatest oxidative stress, with early tumor cell injury affecting the cytoskeletal architecture and contributing to the self-excisions of pieces of cytoplasm freed from organelles. Additional damage, including a reduction in cell size, organelle alterations, nuclear damage, and nucleic acid degradation as well as compromised lysosome integrity, is caused by reactivation of DNases and the redox cycling of VC or VCVK3. In addition, cell death caused by VCVK3 treatment as well as by prolonged VC treatment is consistent with cell demise by autoschizis, not apoptosis. This report confirms and complements previous observations about this new mode of tumor cell death. It supports the contention that a combination of VCVK3, also named Apatone, could be co-administered as a nontoxic adjuvant with radiation and/or chemotherapies to kill bladder tumor cells and other cancer cells without any supplementary risk or side effects for patients.
AB - A human bladder carcinoma cell line RT4 was sham-treated with buffer or treated with ascorbate (VC) alone, menadione alone (VK3), or a combination of ascorbate:menadione (VCVK3) for 1, 2, and 4h. Cytotoxic damage was found to be treatment-dependent in this sequence: VCVK3>VC>VK3>sham. The combined treatment induced the greatest oxidative stress, with early tumor cell injury affecting the cytoskeletal architecture and contributing to the self-excisions of pieces of cytoplasm freed from organelles. Additional damage, including a reduction in cell size, organelle alterations, nuclear damage, and nucleic acid degradation as well as compromised lysosome integrity, is caused by reactivation of DNases and the redox cycling of VC or VCVK3. In addition, cell death caused by VCVK3 treatment as well as by prolonged VC treatment is consistent with cell demise by autoschizis, not apoptosis. This report confirms and complements previous observations about this new mode of tumor cell death. It supports the contention that a combination of VCVK3, also named Apatone, could be co-administered as a nontoxic adjuvant with radiation and/or chemotherapies to kill bladder tumor cells and other cancer cells without any supplementary risk or side effects for patients.
KW - Autoschizis
KW - Bladder carcinoma
KW - Cell death
KW - RT4
KW - Tumor cell
UR - http://www.scopus.com/inward/record.url?scp=77952272321&partnerID=8YFLogxK
U2 - 10.3109/01913121003662304
DO - 10.3109/01913121003662304
M3 - Article
C2 - 20455663
AN - SCOPUS:77952272321
SN - 0191-3123
VL - 34
SP - 140
EP - 160
JO - Ultrastructural Pathology
JF - Ultrastructural Pathology
IS - 3
ER -