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

Emiko L. Hatcher, Judith M. Alexander, Yujian Kang

Research output: Contribution to journalArticle

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Abstract

Cross-resistance presents an obstacle in cancer chemotherapy. Cadmium is a potential carcinogen whose exposure has been shown in epidemiological and laboratory experiments to cause lung cancer. Cadmium also induces various forms of resistance in human lung carcinoma cells. This resistance may be shared by antineoplastic agents, which should be a concern for chemotherapy of cadmium-induced lung cancer. In the present study, two subpopulations of human lung carcinoma A549 cells with a different magnitude of resistance to cadmium toxicity were shown to have a parallel resistance to the cytotoxic action of Adriamycin (ADR), an important anticancer drug. Several factors were examined to investigate the mechanism(s) for the cross-resistance, including cellular metallothionein and glutathione (GSH) concentrations, glutathione S-transferase activity, mdr1 expression, and antioxidant enzyme activities including superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Only cellular GSH content was elevated consistently in the cadmium/ADR-resistant cells relative to the cadmium/ADR-sensitive cells. Treatment with buthionine sulfoximine, a specific inhibitor of GSH synthesis sensitized both cell lines to ADR only when the cellular GSH levels were depleted to about 5% of control. This BSO treatment, however, did not affect cell viability. Further study revealed that the cadmium/ADR-resistant cells have a greater capacity in recovery of cellular GSH content following BSO treatment. The results demonstrate that cross-resistance to ADR exists in cadmium-resistant human lung carcinoma A549 cells, and enhanced GSH synthesis capacity, rather than elevated levels of cellular GSH, may be related to this resistance.

Original languageEnglish (US)
Pages (from-to)747-754
Number of pages8
JournalBiochemical Pharmacology
Volume53
Issue number5
DOIs
StatePublished - Mar 7 1997
Externally publishedYes

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Cadmium
Doxorubicin
Carcinoma
Lung
Chemotherapy
Cells
Lung Neoplasms
Buthionine Sulfoximine
Drug Therapy
A549 Cells
Glutathione Reductase
Metallothionein
Enzyme activity
Glutathione Peroxidase
Glutathione Transferase
Carcinogens
Antineoplastic Agents
Catalase
Superoxide Dismutase
Glutathione

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Decreased sensitivity to adriamycin in cadmium-resistant human lung carcinoma A549 cells. / Hatcher, Emiko L.; Alexander, Judith M.; Kang, Yujian.

In: Biochemical Pharmacology, Vol. 53, No. 5, 07.03.1997, p. 747-754.

Research output: Contribution to journalArticle

Hatcher, Emiko L. ; Alexander, Judith M. ; Kang, Yujian. / Decreased sensitivity to adriamycin in cadmium-resistant human lung carcinoma A549 cells. In: Biochemical Pharmacology. 1997 ; Vol. 53, No. 5. pp. 747-754.
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