Manganese superoxide dismutase content and localization in human thyroid tumours

Nishida, Shozo; Akai, Fumiharu; Iwasaki, H; Hosokawa, Koichi; Kusunoki, Takeshi; Suzuki, Kaho; Taniguchi, Naoyuki; Hashimoto, Shigeo; Tt, Tamura

doi:10.1002/path.1711690311

Cited by 45 publications

(34 citation statements)

References 19 publications

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“…However, the role of MnSOD in tumours is more complicated than originally assumed. Recent studies have detected high MnSOD levels in colon cancer (Nakano et al, 1996), thyroid cancer (Nishida et al, 1996) and tumours of central nervous origin (Cobbs et al, 1996;Landriscina et al, 1996), and our data on M38K (Kinnula et al, 1996). Tumours may have high immunoreactive protein without elevated enzyme activity, but our mesothelioma cells also demonstrated elevated specific activity of MnSOD (Kinnula et al, 1996).…”

Section: Discussionsupporting

confidence: 60%

Endogenous antioxidant enzymes and glutathione S-transferase in protection of mesothelioma cells against hydrogen peroxide and epirubicin toxicity

Kinnula

Linnainmaa²,

Ko³

et al. 1998

Br J Cancer

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Summary We have previously shown that cultured malignant mesothelioma cells contain elevated manganese superoxide dismutase (MnSOD) mRNA levels and activities compared with non-malignant mesothelial cells. As many cytotoxic drugs generate both superoxide and hydrogen peroxide, we assessed the relative significance of catalase and the glutathione redox cycle, as well as glutathione S-transferase (GST), in protecting these cells against hydrogen peroxide and epirubicin toxicity. Mesothelioma cell lines containing high (M38K cells) and low (M14K cells) MnSOD, and non-malignant MeT-5A mesothelial cells were selected for the study. M38K cells were the most resistant of these three cell types to hydrogen peroxide (0.1-0.5 mm, 4 h) and epirubicin (0.1-0.5,g ml-', 48 h) as judged by lactate dehydrogenase (LDH) release and by high-energy nucleotide (ATP, ADP, AMP) depletion. Total glutathione was higher in M38K cells (63.8 ± 20.3 nnmol mg-1 protein) than in M14K (25.2 ± 8.2 nmol mg-') or MeT-5A cells (23.5 ± 4.5 nmol mg-'). Furthermore, GST specific activity was higher in M38K cells (111.3 ± 15.8 U mg-') than in M14K cells (77.4 ± 6.6 U mg-') or in MeT-5A cells (68.8 ± 7.6 U mg-'). Western blotting indicated the presence of GST-i in all these cells, the reactivity again being highest in M38K cells. Depletion of glutathione by buthionine sulphoximine and inhibition of catalase by aminotriazole enhanced hydrogen peroxide toxicity in all cell types, while only the depletion of glutathione increased epirubicin toxicity. We conclude that simultaneous induction of multiple antioxidant enzymes can occur in human mesothelioma cells. In addition to the high MnSOD activity, hydrogen peroxide scavenging antioxidant enzymes, glutathione and GST can partly explain the high hydrogen peroxide and epirubicin resistance of these cells in vitro.

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Section: Discussionsupporting

confidence: 60%

Endogenous antioxidant enzymes and glutathione S-transferase in protection of mesothelioma cells against hydrogen peroxide and epirubicin toxicity

Kinnula

Linnainmaa²,

Ko³

et al. 1998

Br J Cancer

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“…These findings suggest that the Mn-SOD gene could behave as a potential tumor suppressor gene [10, 11, 12, 13, 14, 15, 16]. Conflicting reports, however, have shown that higher Mn-SOD expression is present in the sera or tumor tissues of patients with cancers of the ovary, thyroid, uterus, brain and some leukemias [17, 18, 19, 20, 21]. Thus, the significance of Mn-SOD expression in malignant tumors remains controversial and requires further study.…”

Section: Introductionmentioning

confidence: 82%

“…The concept of ‘tumor suppression’ function of Mn-SOD has recently been challenged by showing higher Mn-SOD expression and/or activity in cancer cells [17, 18, 19, 20, 21]. For example, Izutani et al [31]examined the expression of Mn-SOD mRNA in gastric carcinomas by RT-PCR and showed significantly higher levels of Mn-SOD expression in cancer tissue than in noncancerous tissue.…”

Section: Discussionmentioning

confidence: 99%

Reduced Expression of Manganese Superoxide Dismutase mRNA May Correlate with Invasiveness in Esophageal Carcinoma

et al. 2000

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Little is known about the expression and antioxidant function of manganese superoxide dismutase (Mn-SOD) in esophageal squamous cell carcinoma. To determine the significance of Mn-SOD in esophageal squamous cell carcinomas, Mn-SOD mRNA expression was examined in 45 esophageal squamous cell carcinomas and the corresponding normal mucosal tissues by reverse transcription-polymerase chain reaction. The tumor/normal (T/N) ratio of 45 patients with esophageal carcinoma was calculated, and the data were clinicopathologically analyzed. The T/N ratio of Mn-SOD mRNA expression was less than 0.5 in 11 (32.4%) of 34 esophageal carcinoma cases without any preoperative treatments, while none of 11 cases who underwent preoperative chemotherapy showed a T/N ratio of <0.5 (p < 0.05). There was an inverse correlation between the Mn-SOD expression level and the degree of venous invasion (p < 0.05) as well as lymphatic invasion (p < 0.05). Furthermore, poorly differentiated squamous cell carcinoma showed significantly lower Mn-SOD mRNA expression levels than well differentiated carcinoma (p < 0.05). Our results suggest that Mn-SOD mRNA was frequently reduced in esophageal carcinoma when compared to the normal mucosa and the reduced expression levels of Mn-SOD mRNA may lead to an accumulation of superoxide radicals in conjunction with the increased invasiveness of esophageal carcinoma.

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“…Although many studies have shown that MnSOD is lower in malignant tissue and malignant cells than in their non-malignant counterparts (Sun, 1990), MnSOD has been shown to be high in human thyroid tumours (Nishida et al, 1993), human renal adenocarcinoma of granular cell type (Oberley et al, 1994), human brain tumours (Cobbs et al, 1996) and human malignant mesothelioma (Kahlos et al, 1998) as compared to corresponding non-malignant control tissues. The mesothelioma tumour biopsies and cell lines used in our studies are from untreated mesothelioma patients.…”

Section: Discussionmentioning

confidence: 98%

Generation of reactive oxygen species by human mesothelioma cells

et al. 1999

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Malignant mesothelioma cells contain elevated levels of manganese superoxide dismutase (MnSOD) and are highly resistant to oxidants compared to non-malignant mesothelial cells. Since the level of cellular free radicals may be important for cell survival, we hypothesized that the increase of MnSOD in the mitochondria of mesothelioma cells may alter the free radical levels of these organelles. First, MnSOD activity was compared to the activities of two constitutive mitochondrial enzymes; MnSOD activity was 20 times higher in the mesothelioma cells than in the mesothelial cells, whereas the activities of citrate synthase and cytochrome c oxidase did not differ significantly in the two cell lines. This indicates that the activity of MnSOD per mitochondrion was increased in the mesothelioma cells. Superoxide production was assayed in the isolated mitochondria of these cells using lucigenin chemiluminescence. Mitochondrial superoxide levels were significantly lower (72%) in the mesothelioma cells compared to the mesothelial cells. Oxidant production in intact cells, assayed by fluorimetry using 2′,7′-dichlorodihydrofluorescein as a fluorescent probe, did not differ significantly between these cells. We conclude that mitochondrial superoxide levels are lower in mesothelioma cells compared to nonmalignant mesothelial cells, and that this difference may be explained by higher MnSOD activity in the mitochondria of these cells. Oxidant production was not different in these cells, which may be due to the previously observed increase in H 2 O 2 -scavenging mechanisms of mesothelioma cells. © 1999 Cancer Research Campaign

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Manganese superoxide dismutase content and localization in human thyroid tumours

Cited by 45 publications

References 19 publications

Endogenous antioxidant enzymes and glutathione S-transferase in protection of mesothelioma cells against hydrogen peroxide and epirubicin toxicity

Endogenous antioxidant enzymes and glutathione S-transferase in protection of mesothelioma cells against hydrogen peroxide and epirubicin toxicity

Reduced Expression of Manganese Superoxide Dismutase mRNA May Correlate with Invasiveness in Esophageal Carcinoma

Generation of reactive oxygen species by human mesothelioma cells

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