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Zinc is a potential therapeutic for chemoresistant ovarian cancer
Max Bastow1, Christopher L Kriedt, Joseph Baldassare
1St. Louis University Medical School, 1402 S. Grand Blvd, St. Louis, MO 63104, USA.
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.
Insights
Zinc demonstrates therapeutic potential against ovarian cancer, showing time and concentration-dependent cytotoxicity. Its distinct killing mechanism offers a promising alternative for drug-resistant ovarian cancers.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Ovarian cancer is a leading cause of gynecological cancer mortality.
- Limited early diagnosis and treatment options contribute to high mortality rates.
- Zinc exhibits cytotoxic properties with therapeutic potential.
Purpose of the Study:
- To investigate the cytotoxic effects of zinc on ovarian cancer cell lines.
- To determine if zinc's mechanism of action differs from current chemotherapeutics.
- To evaluate zinc as a potential treatment for drug-resistant ovarian cancer.
Main Methods:
- Utilized SKOV3 and ES2 ovarian cancer cell lines.
- Assessed zinc-induced cytotoxicity in a time- and concentration-dependent manner.
- Compared zinc's effects with cisplatin, doxorubicin, and paclitaxel.
Main Results:
- Zinc-induced cell death was time and concentration-dependent, preceded by morphological changes.
- Zinc's effects were additive with cisplatin and doxorubicin but distinct morphologically.
- Paclitaxel showed minimal cytotoxicity, with similar but mechanistically different morphological effects compared to zinc.
Conclusions:
- Zinc exhibits a distinct mechanism of killing ovarian cancer cells compared to current chemotherapeutics.
- Zinc's cytotoxic properties suggest potential as a primary or secondary treatment.
- Zinc may offer a novel therapeutic strategy for chemoresistant ovarian cancers.
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