title: Zinc is a potential therapeutic for chemoresistant ovarian cancer.
abstract: Ovarian cancer is the leading cause of death from gynecological cancer. The high mortality rate reflets the lack of early diagnosis and limited treatment alternatives. We have observed a number of properties of zinc cytotoxicity that make it attractive from a therapeutic standpoint. Using SKOV3 and ES2 cells, ovarian cancer cell lines that demonstrate varied degrees of resistance to known therapeutics, we show that zinc killing is time and concentration dependent. Death is preceded by distinct changes in cell shape and size. The effects of zinc are additive with cisplatin or doxorubicin, whose morphological effects are distinct from those of zinc. Cytotoxicity of paclitaxel is minimal, making it difficult to determine additivity with zinc. Paclitaxel results in changes in cell shape and size similar to those of zinc but has different effects on cell cycle progression and cyclin expression. The data indicate that the means by which zinc kills ovarian cancer cells is distinct from currently used chemotherapeutics. Based on the properties reported here, zinc has the potential to be developed as either a primary treatment or as a second line of defense against cancers that have developed resistance to currently used chemotherapeutics.
authors: St. Louis University Medical School, 1402 S. Grand Blvd, St. Louis, MO 63104, USA.
authors: Max
authors: M
authors: Bastow
authors: Christopher L
authors: CL
authors: Kriedt
authors: Joseph
authors: J
authors: Baldassare
authors: Maulik
authors: M
authors: Shah
authors: Claudette
authors: C
authors: Klein
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019925:Cyclin A / Q000187:drug effects / Q000378:metabolism; D056741:Cyclin D / Q000187:drug effects / Q000378:metabolism; D019927:Cyclin E / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D013871:Thiones / Q000494:pharmacology; D014131:Trace Elements / Q000494:pharmacology*; D015032:Zinc / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D019925:Cyclin A; D056741:Cyclin D; D019927:Cyclin E; D011725:Pyridines; D013871:Thiones; D014131:Trace Elements; C008704:pyrithione; D004317:Doxorubicin; D015032:Zinc; D017239:Paclitaxel; D002945:Cisplatin