Anti-cancer agent OK432 induces manganese superoxide dismutase in human granulocytes

Akashi, Makoto; Takagi, Sayoko; Hachiya, Misao

doi:10.1002/(sici)1097-0215(19961104)68:3<384::aid-ijc18>3.0.co;2-8

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…They did not measure immunoreactive protein or Mn SOD activity or effects of Mn SOD induction on the oxidant or drug resistance. The results of our and other recent studies (1,9,11) cannot rule out the possibility that Mn SOD activity may also be induced by cytotoxic drugs in vivo.…”

Section: Discussioncontrasting

confidence: 91%

“…Few studies have investigated Mn SOD induction by cytotoxic drugs. Akashi et al (1) have shown that the anticancer drug OK-432 leads to elevation of Mn SOD in human granulocytes. Das and White (11) showed that anticancer drugs such as paclitaxel, vinca alkaloids (vinblastine and vincristine), and anthracyclines (daunomycin and doxorubicin) may cause activation of nuclear factor-B, and recently, Das et al (9) also reported that mRNA of Mn SOD was upregulated by cytotoxic drugs through a protein kinase-dependent mechanism.…”

Section: Discussionmentioning

confidence: 99%

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Antioxidant defense mechanisms of human mesothelioma and lung adenocarcinoma cells

Järvinen

Pietarinen-Runtti

Linnainmaa

et al. 2000

American Journal of Physiology-Lung Cellular and Molecular Phys

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The development of drug resistance of tumors is multifactorial and still poorly understood. Some cytotoxic drugs generate free radicals, and, therefore, antioxidant enzymes may contribute to drug resistance. We investigated the levels of manganese superoxide dismutase (Mn SOD), its inducibility, and its protective role against tumor necrosis factor-alpha and cytotoxic drugs (cisplatin, epirubicin, methotrexate, and vindesin) in human pleural mesothelioma (M14K) and pulmonary adenocarcinoma (A549) cells. We also studied other major antioxidant mechanisms in relation to oxidant and drug resistance of these cells. A549 cells were more resistant than M14K cells toward both oxidants (hydrogen peroxide and menadione) and all the cytotoxic drugs tested. M14K cells contained higher basal Mn SOD activity than A549 cells (28.3 +/- 3.4 vs. 1.8 +/- 0.3 U/mg protein), and Mn SOD activity was significantly induced by tumor necrosis factor-alpha only in A549 cells (+524%), but the induction did not offer any protection during subsequent oxidant or drug exposure. Mn SOD was not induced significantly in either of these cell lines by any of the cytotoxic drugs (0.007-2 microM, 48 h) tested when assessed by Northern blotting, Western blotting, or specific activity. A549 cells contained higher catalase activity than M14K cells (7.6 +/- 1.3 vs. 3.6 +/- 0.5 nmol O(2). min(-1). mg protein(-1)). They also contained twofold higher levels of glutathione and higher immunoreactivity of the heavy subunit of gamma-glutamylcysteine synthetase than M14K cells. Experiments with inhibitors of gamma-glutamylcysteine synthetase and catalase supported our conclusion that mechanisms associated with glutathione contribute to the drug resistance of these cells.

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Section: Discussioncontrasting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Antioxidant defense mechanisms of human mesothelioma and lung adenocarcinoma cells

Järvinen

Pietarinen-Runtti

Linnainmaa

et al. 2000

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…21 OK432 is reported to be effective in promoting the production of IL-1 and tumor necrosis factor (TNF)-α by neutrophils. 35 Accordingly, in this study, significant increases in intraperitoneal IL-, MIP-1α, and IL-6 corresponded with neutrophil accumulation. It appears that these cytokines and chemokines not only perform important functions in the intraperitoneal accumulation of lymphocytes and macrophages, 36 but also act on inflammatory cells and tumor cells to induce the expression of adhesion molecules such as ICAM-1 and CD11b/CD18, 37 leading to the acquisition of specific tumor immunity.…”

Section: Discussionsupporting

confidence: 59%

Effect of Intraperitoneal Neutrophils Induced by OK432 on Malignant Ascites

et al. 2005

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“…The basal expression of MnSOD is usually low, often hardly detectable, but the enzyme is induced by hyperoxia10, irradiation12, cytokines such as tumour necrosis factor13, interleukins14 and interferon15, and changes in the cellular redox state16. Recently, up‐regulation of MnSOD has also been shown to occur in response to the exposure to various cytotoxic drugs, at least in human lung adenocarcinoma cells and human granulocytes17, 18. Several, but not all, studies have also emphasized the importance of superoxide dismutase in the protection of cells and tissues against hyperoxia, cytokines and possibly cytotoxic drugs, both in vitro and in vivo 13, 19–23.…”

Section: Introductionmentioning

confidence: 99%

MnSOD expression is less frequent in tumour cells of invasive breast carcinomas than inin situcarcinomas or non-neoplastic breast epithelial cells

et al. 2001

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Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme capable of neutralizing superoxide anion molecules. In previous studies it has been suggested to suppress both tumour proliferation and apoptosis. This study investigated 65 invasive, 50 in situ and 19 benign hyperplastic breast lesions for its immunohistochemical expression. MnSOD expression was also tested with in situ hybridization. To study cell proliferation, apoptosis and their association with MnSOD expression the neoplastic breast lesions were immunostained with a monoclonal antibody to Ki-67 and the extent of apoptosis in them was determined by the TUNEL method. 32/65 (49%) of the invasive ductal carcinomas, 41/50 (82%) of the in situ and 15/19 (79%) of the benign hyperplasias expressed the MnSOD protein. There were significantly more MnSOD positive cases in in situ carcinoma and in benign hyperplasia than in invasive carcinoma (p=0.00016 and p=0.022, respectively). Positivity was also more frequently found in non-neoplastic ductal and acinar epithelial cells than in invasive carcinoma. On the other hand, neoplastic epithelial cells of invasive and in situ carcinoma showed strong positivity more often than the epithelial cells of benign hyperplasia or non-neoplastic epithelium. In breast lesions, MnSOD positivity did not associate with proliferation or apoptosis. The lower frequency of MnSOD positive cases in invasive breast carcinoma suggests that the lack of its expression might contribute to the development of an invasive breast carcinoma phenotype and that it could in this way operate as a tumour suppressor gene, as previously suggested.

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Anti-cancer agent OK432 induces manganese superoxide dismutase in human granulocytes

Cited by 6 publications

References 25 publications

Antioxidant defense mechanisms of human mesothelioma and lung adenocarcinoma cells

Antioxidant defense mechanisms of human mesothelioma and lung adenocarcinoma cells

Effect of Intraperitoneal Neutrophils Induced by OK432 on Malignant Ascites

MnSOD expression is less frequent in tumour cells of invasive breast carcinomas than inin situcarcinomas or non-neoplastic breast epithelial cells

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