Decreased sensitivity to adriamycin in cadmium-resistant human lung carcinoma A549 cells

Hatcher, Emiko L.; Alexander, Judith M.; Kang, Y. James

doi:10.1016/s0006-2952(96)00811-8

Cited by 13 publications

(5 citation statements)

References 26 publications

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“…A recent report (43) has shown that the ␥-GCS light subunit, which exerts regulatory control over ␥-GCS enzyme activity, maps within a critically deleted region of human malignant mesothelioma. On the basis of our laboratory's (22) and other studies (2,14,21), we conclude that glutathione metabolism is important in the resistance of lung adenocarci-noma and human malignant mesothelioma cells against oxidants and oxidant-generating cytotoxic drugs.…”

Section: Discussionmentioning

confidence: 71%

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: Discussionmentioning

confidence: 71%

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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“…(Lieber et al 1976;Foster et al 1998;Hukkanen et al 2000). Concurrently, some cell subpopulations with distinct features have been identified in the original heterogeneous cell population (Hatcher et al 1997;Croce et al 1999). What is more, this cell line displays characteristic mutations in tumor-suppressor genes, i.e., p16 INK4a , p14 ARF and p15 INK4b homozygous deletions, which are common in many cancers (Okamoto et al 1995;Iavarone and Massagué 1997;Edelman et al 2001;Xie et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Features of senescence and cell death induced by doxorubicin in A549 cells: organization and level of selected cytoskeletal proteins

Litwiniec

Grzanka

Helmin-Basa

et al. 2009

J Cancer Res Clin Oncol

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“…3,4 Although this approach, using the anthracyclines, has not been successful, 5,6 the understanding of the interactions between these antitumor compounds and metal ions, especially biometals, such as Fe 3+ , could be very useful to elucidate the molecular mechanisms in terms of biological activity and cell resistance. 7 In fact, it has been suggested that the adduct formation between anthracyclines and DNA [8][9][10] or phospholipids 11 could be enhanced by the presence of Fe 3+ . Furthermore, the interaction between Fe 3+ and anthracyclines could alter the antitumor properties of the drugs.…”

Section: Introductionmentioning

confidence: 99%

“…The development of multidrug resistance (MDR) against anthracyclines (Figure ), as well as against other antitumor compounds, is a major problem in anticancer chemotherapy. Complexation of metal ions to biologically active molecules has been recently proposed as a new strategy to overcome the drug resistance. , Although this approach, using the anthracyclines, has not been successful, , the understanding of the interactions between these antitumor compounds and metal ions, especially biometals, such as Fe 3+ , could be very useful to elucidate the molecular mechanisms in terms of biological activity and cell resistance . In fact, it has been suggested that the adduct formation between anthracyclines and DNA − or phospholipids could be enhanced by the presence of Fe 3+ .…”

Section: Introductionmentioning

confidence: 99%

Solution Structure of Iron(III)−Anthracycline Complexes

et al. 1999

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The interaction of Fe(3+) with the anthracycline anticancer drug idarubicin (Ida) was studied by absorption, CD, Mössbauer, and EPR spectroscopy. The formation of two major Fe(3+)-Ida complexes, labeled I and II, was observed. In complex I, Fe(3+) ion was bound to anthracycline at the {C(12)=O; C(11)-O(-)} coordination site. In complex II, two Fe(3+) ions were bound at sites {C(5)=O; C(6)-O(-)} and {C(12)=O; C(11)-O(-)}, respectively. Complex I was an equimolar monomeric species with a 1:1 Fe(3+):Ida stoichiometry (beta(1) = 4.8 x 10(11) M(-1)), whereas in complex II the anthracycline ligand was bridging two metal ions, alternatively bound to both anthracycline ring chelating sites with the assumption that the ratio of Fe(3+):Ida in complex II was 2:1 (beta(2) = 5.3 x 10(24) M(-2)). Alternatively, complex II may be oligomeric with Fe(3+):Ida = 1:1 and with each Fe(3+) bridging two Ida molecules. Our findings could be important in understanding the biological effects of the anthracycline-ferric complexes. Thus, providing information about the nature of the Fe(3+)-Ida system, we suggest that the formal 1:3 Fe(3+):anthracycline complexes, reported in the previous literature, could be a mixture of species I, II, and free ligand.

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Decreased sensitivity to adriamycin in cadmium-resistant human lung carcinoma A549 cells

Cited by 13 publications

References 26 publications

Antioxidant defense mechanisms of human mesothelioma and lung adenocarcinoma cells

Antioxidant defense mechanisms of human mesothelioma and lung adenocarcinoma cells

Features of senescence and cell death induced by doxorubicin in A549 cells: organization and level of selected cytoskeletal proteins

Solution Structure of Iron(III)−Anthracycline Complexes

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