A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells

Borrelli, Antonella; Schiattarella, Antonella; Mancini, R. E.; Morrica, Brunello; Cerciello, Vincenzo; Mormile, M.; D'Alesio, V.; Bottalico, Laura; Morelli, Francesco; D’Armiento, Maria; D’Armiento, Francesco Paolo; Mancini, Aldo

doi:10.1016/j.freeradbiomed.2008.10.030

Cited by 47 publications

(30 citation statements)

References 29 publications

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“…Substantial studies have demonstrated that increasing ROS and down-regulating SOD and GSH activities after radiotherapy can accomplish the sensitization of radiotherapy [17]. However, Antonella et al [18] pointed out that the upregulation of antioxidant expression can enhance the radiosensitivity of tumor cells, while protect healthy tissues from the radiation; our research reached similar findings. Our findings suggest that the antioxidant effects of SSd are capable of regulating intracellular oxidative stress and scavenging free oxygen radicals.…”

Section: Discussionsupporting

confidence: 84%

Effects of SSd Combined with Radiation on Inhibiting SMMC-7721 Hepatoma Cell Growth

et al. 2014

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BackgroundThe aim of this study was to investigate the effects of Saikosaponin-d (SSd) combined with radiotherapy on SMMC-7721 hepatoma cell lines and its mechanism.Material/MethodsSMMC-7721 hepatoma cell lines are selected in our research. With MTT (methylthiazolyldiphenyl-tetrazolium-bromide) method, the effects of SSd and radiation on inhibiting SMMC-7721 cell growth were investigated. We also used transmission electron microscopy (TEM) to observe ultrastructural changes of cells. Colorimetry methods were used to measure content changes of glutathione (GSH) and malondialdehyde (MDA) in cells.ResultsBoth SSd and radiation inhibited the growth of SMMC-7721 cells. The combination of SSd and radiotherapy had a time-dependent synergistic effect. Radiation caused ultrastructural damage to cells, and the damage was enhanced in combination with SSd. Radiation decreased the GSH content and increased the MDA content in cells, and this effect was suppressed after the intervention of SSd.ConclusionsSSd can inhibit the growth of SMMC-7721 hepatoma cell lines in vitro. Additionally, it significantly enhances the effects of radiation on inhibiting the growth of SMMC-7721 hepatoma cell lines, and up-regulates the antioxidant level after the radiotherapy. Thus, SSd could be an ideal radiotherapy sensitizer for the treatment of liver cancer.

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Section: Discussionsupporting

confidence: 84%

Effects of SSd Combined with Radiation on Inhibiting SMMC-7721 Hepatoma Cell Growth

et al. 2014

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“…Radiosensitivity was determined according to the method described by Matthew and Antonella (Ough et al, 2004;Borrelli et al, 2009). Cells were plated in 96-well plates at a density that would allow cells to reach 70-75% confluency within 24 h. These cells were then separately treated with SNP (0-4 mmol/L), radiation (0-6 Gy of X-rays, linear accelerator, Elekta, Sweden), or 1 mmol/L SNP combined with 2 Gy radiation and allowed to grow for 48 h. After 48 h of culture, 20 μl assay medium containing 5 mg/ml MTT was added to each well and incubated at 37 ºC for 4 h. The medium was gently aspirated, and then 150 μl DMSO was added to each well to solubilize the formazan crystals.…”

Section: Radiosensitivity Analysismentioning

confidence: 99%

Bidirectional Regulation of Manganese Superoxide Dismutase (MnSOD) on the Radiosensitivity of Esophageal Cancer Cells

Sun

Hu²,

Wang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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The mitochondrial antioxidant protein manganese superoxide dismutase (MnSOD) may represent a new type of tumor suppressor protein. Overexpression of the cDNA of this gene by plasmid or recombinant lentiviral transfection in various types of cancer leads to growth suppression both in vitro and in vivo. We previously determined that changes in MnSOD expression had bidirectional effects on adriamycin (ADR) when combined with nitric oxide (NO). Radiation induces free radicals in a manner similar to ADR, so we speculated that MnSOD combined with NO would also have a bidirectional effect on cellular radiosensitivity. To examine this hypothesis, TE-1 human esophageal squamous carcinoma cells were stably transfected using lipofectamine with a pLenti6-DEST plasmid containing human MnSOD cDNA at moderate to high overexpression levels or with no MnSOD insert. Blastidicin-resistant colonies were isolated, grown, and maintained in culture. We found that moderate overexpression of MnSOD decreased growth rates, plating efficiency, and increased apoptosis. However, high overexpression increased growth rates, plating efficiency, and decreased apoptosis. When combined with NO, moderate overexpression of MnSOD increased the radiosensitivity of esophageal cancer cells, whereas high MnSOD overexpression had the opposite effect. This finding suggests a potential new method to kill certain radioresistant tumors and to provide radioresistance to normal cells.

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“…In addition, the recombinant form of LSA-MnSOD (rMnSOD) not only exerts the same radioprotective ef-fect on normal cells and organisms as any other MnSOD, but it also exerts a radiosensitizing action on tumor cells. It was also demonstrated that healthy mice, exposed to lethal doses of ionizing radiation and to daily injections of rMnSOD, were protected from radiation damage and were still alive 30 days after the X ray, while the controls injected only with PBS solution, died 7 -8 days later [5]. The remarkable ability of rMnSOD to neutralize free radicals, that occur in damaged tissues, has also been demonstrated by the complete recovery from a severe necrosis of the head, neck, and fins of a specimen of loggerhead sea turtle Caretta caretta.…”

Section: Introductionmentioning

confidence: 99%

“…The skin has an enzyme system which minimizes the damaging effect of ROS and helps to maintain the homeostatic balance, such as glutathione reductase, catalase, and superoxide dismutase. The superoxide dismutases (SODs) are enzymes of remarkable pharmacological interest for their potential role in the prevention of all the pathologies caused by oxidative damage [5]. SODs are involved in antioxidant defense in almost all cells, since they catalyze the dismutation of superoxide radical into hydrogen peroxide, which is subsequently converted to water and oxygen by the enzyme catalase [6].…”

Section: Introductionmentioning

confidence: 99%

Effects of a New Human Recombinant MnSOD in the Treatment of Photoaging and Actinic Keratosis

Ruggiero¹,

Pollio²,

Schiattarella³

et al. 2013

JCT

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Physiological processes, as aerobic metabolism and inflammatory response, generate reactive oxygen species (ROS) that may induce cellular injury when their amount is increased and antioxidant defense mechanisms are overwhelmed. Also, ROS are generated following UV skin irradiation able to deplete the natural antioxidant defenses in the skin. The increase in exposure to UV may lead to photoaging and precancerous skin lesions (actinic keratosis). New antioxidant strategies in the prevention and therapy of skin lesions are urgently needed. In this study, we evaluated the antioxidant efficacy of a recombinant form of human manganese superoxide dismutase able to inhibit reactive oxygen species production in some patients affected by severe photoaging and actinic keratosis.

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A recombinant MnSOD is radioprotective for normal cells and radiosensitizing for tumor cells

Cited by 47 publications

References 29 publications

Effects of SSd Combined with Radiation on Inhibiting SMMC-7721 Hepatoma Cell Growth

Effects of SSd Combined with Radiation on Inhibiting SMMC-7721 Hepatoma Cell Growth

Bidirectional Regulation of Manganese Superoxide Dismutase (MnSOD) on the Radiosensitivity of Esophageal Cancer Cells

Effects of a New Human Recombinant MnSOD in the Treatment of Photoaging and Actinic Keratosis

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