Differential cytotoxicity of trace metals in cisplatin-sensitive and -resistant human ovarian cancer cells. 1998

D L Nicholson, and S M Purser, and R H Maier
Department of Surgery, East Carolina University, Greenville, NC 27858, USA.

Cellular resistance of cisplatin is related to various factors such as membrane transformations, changes in cellular transport systems, and an increased efflux of cisplatin by the tumor cells. Deficiencies of one or more trace metals can affect normal physiological functions, leading to altered enzymatic activities and a reduction in immune responses. This in vitro investigation was undertaken to study and determine the differential cytotoxicity of certain trace metals in human ovarian cancer cells that were sensitive and resistant to cisplatin. Standard cytotoxicity assays were performed using the neutral red assay. In general, the cisplatin-resistant cells exhibited an increased resistance to the externally supplied trace metals. For both cell lines the rank order of cytotoxicity from greatest to least with the non-essential metals was Cd2+ > Bi3+, and for the macrometals, Ca2+ > K+ > Mg2+. The transition metals and selenium exhibited a slight difference between the two cell lines with respect to the order of cytotoxicity. The cisplatin-sensitive cells had a rank order of V5+ > Se6+ > Cu2+ > Zn2+ > Fe3+, from greatest to least toxicity. The cisplatin-resistant cells had a rank order of Cu2+ > V5+ > Se6+ > Zn2+ > Fe3+. Since trace metals have various functions in maintaining normal health, these results provide key baseline cytotoxicity data and show that, in general, cytotoxic resistance to the trace metals tested followed a pattern similar to cellular cisplatin resistance.

UI MeSH Term Description Entries
D008670 Metals Electropositive chemical elements characterized by ductility, malleability, luster, and conductance of heat and electricity. They can replace the hydrogen of an acid and form bases with hydroxyl radicals. (Grant & Hackh's Chemical Dictionary, 5th ed) Metal
D010051 Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS. Cancer of Ovary,Ovarian Cancer,Cancer of the Ovary,Neoplasms, Ovarian,Ovary Cancer,Ovary Neoplasms,Cancer, Ovarian,Cancer, Ovary,Cancers, Ovarian,Cancers, Ovary,Neoplasm, Ovarian,Neoplasm, Ovary,Neoplasms, Ovary,Ovarian Cancers,Ovarian Neoplasm,Ovary Cancers,Ovary Neoplasm
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D019008 Drug Resistance, Neoplasm Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures. Antibiotic Resistance, Neoplasm,Antineoplastic Drug Resistance,Drug Resistance, Antineoplastic,Antineoplastic Agent Resistance,Neoplasm Drug Resistance,Resistance, Antineoplastic Agent,Resistance, Antineoplastic Drug

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