Suppression of intracellular Cu‐Zn SOD results in enhanced motility and metastasis of Meth A sarcoma cells

Abstract

We have previously described an inverse relationship between Cu-Zn superoxide dismutase (SOD) activity and invasiveness of a clone of human tongue cancer cells. In these cells, suppression of Cu-Zn SOD activity by transfection with anti-sense cDNA enhanced motility in vitro. The present studies were undertaken to determine whether the inverse relationship between intracellular Cu-Zn SOD activity and motility is a general property of other tumor cells and whether this enzyme indeed defines in vivo metastatic potential. Murine Meth A sarcoma-derived ML-01 cells, which have low metastatic activity, were transfected with anti-sense Cu-Zn SOD cDNA. Two clones with very different SOD activities-ML-AS2, with the most suppressed, and ML-AS5, with the least suppressed activity-were analyzed for their motility and metastatic capability. Compared to the mocktransfectant ML-neo, the metastatic potential and motility of the ML-AS2 and ML-AS5 were increased 4.5-and 2.1-fold, respectively. Superoxide treatment enhanced the motility of the AS clones but not that of the ML-neo cells. Our results clearly show that there is an inverse relationship between the intracellular level of Cu-Zn SOD, cell motility and in vivo metastatic potential. Int.

Anti-metastatic gene therapy utilizing subcutaneous inoculation of EC-SOD gene transduced autologous fibroblast suppressed lung metastasis of Meth-A cells and 3LL cells in mice

“…However, it has clearly suppressed metastasis by inhibiting cell motility 11,12 and has been clinically proven not to cause any severe side-effects unless an extremely high dosage has been administered. 18 This non-toxic property is essen-tial in an anti-metastatic agent for clinical use since metastasis occurs continuously and requires constant, longterm suppression.…”

“…11 We also disclosed that superoxide dismutase (SOD), a scavenger of superoxide, counteracts this motility. 11,12 More recently, we disclosed a signaling of protein kinase C to rho family proteins via complex formation with rho GDI as a mechanism underlying the enhanced motility by superoxide (submitted). We also reported the anti-metastatic activity of SOD in both experimental and spontaneous metastatic models with results compatible with the above findings.…”

Inhibitory effect of gingerol on the proliferation and invasion of hepatoma cells in culture

“…Pretreatment of AH109A cells with hypoxanthine and xanthine oxidase or hydrogen peroxide AH109A cells were cultured for 4 h in the absence or presence of 20 lM [6]-gingerol with or without a ROS-generating system, i.e., 4 lg/mL hypoxanthine (HX, Sigma, St. Louis, MO) with 7 9 10 -4 U/mL xanthine oxidase (XO, Sigma) Tanaka et al 1997) or 25 lM hydrogen peroxide (H 2 O 2 , Wako Pure Chemical Industries). AH109A cells were then washed once with 10% CS/MEM and seeded on the M-cell monolayer in 10% CS/MEM without [6]-gingerol and ROS.…”

Inhibitory Effect of Ascorbic Acid on the Proliferation and Invasion of Hepatoma Cells in Culture

“…Pretreatment of AH109A cells with hypoxanthine and xanthine oxidase or hydrogen peroxide AH109A cells were cultured for 4 h in the absence or presence of 62.5 lM AsA with or without a ROS-generating system, i.e., 4 lg/ml hypoxanthine (HX, Sigma, St. Louis, MO) with 7 · 10 À4 U/ ml xanthine oxidase (XO, Sigma) Tanaka et al 1997) or 25 lM hydrogen peroxide (H 2 O 2 , Wako Pure Chemical Industries). AH109A cells were then washed once with 10% CS/MEM and seeded on the M-cell monolayer in 10% CS/MEM without AsA and ROS.…”