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

Tanaka, Maki; Kogawa, Katsuhisa; Nakamura, Kiminori; Nishihori, Yoshiki; Kuribayashi, Kageaki; Hagiwara, Seiya; Muramatsu, Hirohito; Sakamaki, Sumio; Niitsu, Yoshiro

doi:10.1038/sj.gt.3301362

Cited by 24 publications

(17 citation statements)

References 28 publications

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“…Diphenyleneiodonium has been used to inhibit ROS production mediated by NADPH oxidase in various cell types [21,31,32]. Our immunohistochemical results showed that NADPH oxidase is over-expressed in EOC tissues as compared to normal ovarian tissues (Fig.…”

Section: Discussionmentioning

confidence: 70%

“…In this study we sought to determine the effects of inhibiting the generation of ROS by DPI, a well-characterized, potent inhibitor of flavoenzymes including NADPH oxidase, on apoptosis of EOC cells, and whether these effects are associated with SOD3 and HIF-1α expression [30,31]. Diphenyleneiodonium has been used to inhibit ROS production mediated by NADPH oxidase in various cell types [21,31,32].…”

Section: Discussionmentioning

confidence: 99%

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Modulation of redox signaling promotes apoptosis in epithelial ovarian cancer cells

Jiang

Fletcher

Ali-Fehmi

et al. 2011

Gynecologic Oncology

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Objective Epithelial ovarian cancer (EOC) cells are known to be resistant to apoptosis through a mechanism that may involve alteration in their redox balance. NADPH oxidase is a major source of intracellular superoxide, which is converted to the less toxic product by superoxide dismutase (SOD). Superoxide contributes to hypoxia inducible factor (HIF)-1α stabilization. We sought to determine the effects of inhibiting the generation of intracellular reactive oxygen species (ROS) on apoptosis of EOC cells. Methods Diphenyleneiodonium (DPI), an irreversible ROS inhibitor, was used to inhibit the generation of ROS in EOC cell lines, SKOV-3 and MDAH-2774, followed by assessment of apoptosis, NADPH oxidase, SOD3 and HIF-1α expression. A combination of immunohistochemistry, immunoprecipitation/western blot, and real-time RT-PCR were utilized to evaluate the expression of these enzymes in EOC cells as well as normal ovarian tissue and ovarian cancer tissue specimens. Results DPI treatment significantly induced apoptosis in both EOC cell lines as evident by increased caspase-3 activity and TUNEL assay. Additionally, both EOC cell lines were found to express NADPH oxidase, HIF-1α, and SOD3, which were highly sensitive to DPI treatment. DPI treatment resulted in reduced NADPH oxidase, SOD3 and HIF-1α levels. Furthermore, ovarian cancer tissues were found to manifest higher NADPH oxidase levels as compared to normal ovarian tissues. Conclusions These data suggest that lowering oxidative stress, possibly through the inhibition of NADPH oxidase, induces apoptosis in ovarian cancer cells and may serve as a potential target for cancer therapy.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Modulation of redox signaling promotes apoptosis in epithelial ovarian cancer cells

Jiang

Fletcher

Ali-Fehmi

et al. 2011

Gynecologic Oncology

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“…A clinical trial was performed with a topical gel containing liposomally encapsulated recombinant human SOD protein for the treatment of painful Peyronie's disease resulting in a significant pain reduction and high patient satisfaction [47]. Optic neuropathy [48], and neurodegeneration/neurotoxicity [49], ototoxicity [50], arthritis [51,52], cerebral vasospasm [53], tumor growth [54][55][56], liver cholestasis [57], liver damage [58,59], inflammation [60] and erectile dysfunction [61] are some of the experimental diseases where SOD isoforms have shown a notorious recovery of the particular ailment. A most recent approach in gene transfer protocols have focused on a combination of genes or therapies rather than a monogene treatment which have shown improved results for a number of the previously described pathologies [36,46,51,54,56].…”

Section: Other Pathologiesmentioning

confidence: 99%

Current Antioxidant Molecular Therapies for Oxidative Stress-Related Ailments

Ramos-Márquez¹,

Siller-López

2008

CGT

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Oxidative cell damage is a natural occurring phenomenon due to the aerobic conditions where cells are embedded; however, such injury can efficiently be controlled and repaired by the inherent antioxidants of the cell. When the oxidant/antioxidant balance is disrupted towards the former by any chemical, biological or physical insult a pathological state could be developed, therefore, an extensive list of compounds with proved or assumed antioxidants properties has largely been used for improving or restoring the health status. Pharmacological therapies as well as dietary or complementary therapies are continuously being investigated for the counteracting of the harmful or damaging effects of oxidation in cells or tissues. However, critical antioxidant levels are not always achieved at the target damaged cells by these approaches; on the other side, the expression of recombinant antioxidant genes specifically directed to the afflicted cell by gene delivery has shown remarkable results. In this review we summarize the literature focused on some of the current antioxidant molecular pharmacological strategies with particular emphasis to the gene transfer protocols involved in the treatment of oxidative stress-related disorders.

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“…All the techniques have been reported to reverse malignant phenotypes of tumour cells. They are (i) intravenous or subcutaneous administration of recombinant human SOD which substitutes specific amino acid for stable one (Yoshizaki et al, 1994); (ii) intravenous administration of SOD conjugated with a pyran copolymer, for prolongation of its activity (Oda et al, 1989); (iii) addition of exogenous liposomal SOD (Beckman et al, 1988); (iv) intraperiponeal or subcutaneous administration of a selective SOD mimetic molecule of nonpeptidic and low molecular weight (Samlowski et al, 2003); (v) elevation of SOD level by sense cDNA transfection (Safford et al, 1994); (vi) inoculation of fibroblasts that are genetically modified to secrete SOD (Tanaka et al, 2001); (vii) elevation of SOD levels by exposure to a superoxide generator and subsequent isolation of superoxide-resistant cells (FernandezPol et al, 1982); (viii) secondary induction of SOD in tumour ) every day from 2 days before coimplantation to the end of the experiment. All the mice were killed under ether anaesthesia at 28 days after implantation, and serum and tumour tissues were collected for examination.…”

Section: Discussionmentioning

confidence: 99%

Prevention of inflammation-mediated acquisition of metastatic properties of benign mouse fibrosarcoma cells by administration of an orally available superoxide dismutase

Okada

Shionoya²,

Kobayashi

et al. 2006

Br J Cancer

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Weakly tumorigenic and nonmetastatic QR-32 cells derived from a fibrosarcoma in C57BL6 mouse are converted to malignant cells once they have grown after being coimplanted with a gelatine sponge which induces inflammation. We administered a newly developed peroral superoxide dismutase (SOD), oxykine, and as control vehicle, gliadin and saline, starting 2 days before the coimplantation and continued daily throughout the experiment. In the oxykine group, tumour incidence was lower (41%) than in the gliadin or saline group (83 and 79%, respectively). The inhibitory effect of oxykine was lost when an individual component of oxykine was administered, that is, SOD alone and gliadin alone. The effect was also abolished when administered by intraperitoneal route. When perfused in situ with nitroblue tetrazolium, an indicator of superoxide formation, the tumour masses from gliadin and saline groups displayed intense formazan deposition, whereas, those from oxykine group had less deposition. Enzymatic activity of SOD was also increased in oxykine group. Arising tumour cells in gliadin and saline groups acquired metastatic phenotype, but those in oxykine group showed reduced metastatic ability. These results suggested that the orally active SOD derivative prevented tumour progression promoted by inflammation, which is thought to be through scavenging inflammatory cell-derived superoxide anion.

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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

Cited by 24 publications

References 28 publications

Modulation of redox signaling promotes apoptosis in epithelial ovarian cancer cells

Modulation of redox signaling promotes apoptosis in epithelial ovarian cancer cells

Current Antioxidant Molecular Therapies for Oxidative Stress-Related Ailments

Prevention of inflammation-mediated acquisition of metastatic properties of benign mouse fibrosarcoma cells by administration of an orally available superoxide dismutase

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