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Lithium Chloride and Inhibition of Glycogen Synthase Kinase 3β as a Potential Therapy for Serous Ovarian Cancer
  1. Akiva P. Novetsky, MD, MS*,
  2. Dominic M. Thompson, MA,
  3. Israel Zighelboim, MD*,
  4. Premal H. Thaker, MD, MS*,
  5. Matthew A. Powell, MD*,
  6. David G. Mutch, MD* and
  7. Paul J. Goodfellow, PhD*,
  1. *Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, and
  2. Division of Endocrine and Oncologic Surgery, Department of Surgery, Washington University School of Medicine and Siteman Cancer Center, St Louis, MO.
  1. Address correspondence and reprint requests to Akiva P. Novetsky, MD, MS, 4911 Barnes Jewish Plaza, 4th Floor Maternity Bldg, St Louis, MO 63110. E-mail: novetskya@wudosis.wustl.edu.

Abstract

Objective Lithium chloride (LiCl) has been shown to demonstrate anticancer properties at supratherapeutic doses. This study was designed to determine whether LiCl, as a single agent or in combination with cytotoxic agents, reduces ovarian cancer cell growth and metabolic activity at clinically achievable levels.

Methods We studied the effects of LiCl on 2 high-grade serous ovarian cancer cell lines, SKOV3 and OVCA 433, and primary cultures developed from ascitic fluid collected from patients with metastatic high-grade serous ovarian cancer. We assessed proliferation and metabolism using cell cycle analysis, MTT assays, and cellular proliferation and clonogenic potential assays.

Results Treatment with 1 mM LiCl had no effect on the cell cycle distribution or metabolic activity of the SKOV3 and OVCA 433 cell lines. Combination treatment with cisplatin or paclitaxel led to statistically significant decreases in metabolic activity in the OVCA 433 cell line and 50% of cultures investigated. The decreased metabolic activity was not, however, associated with decreased cell growth or clonogenic potential.

Conclusions Combination treatment with LiCl and cytotoxic agents at physiologically achievable drug concentrations reduces ovarian cancer cell metabolism but does not appear to affect cellular proliferation. The potential for combined lithium/cytoxic therapies appears to be limited based on our analysis of both established cell lines and short-term ovarian cancer cultures.

  • Ovarian cancer
  • GSK3-beta
  • Lithium chloride

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Footnotes

  • Funding was received from Barnes-Jewish Hospital Foundation Special Research Program Grant (7519-55) Support for Gynecologic Oncology Research and Jane Eberle-Newbold Memorial Fund.

  • The authors declare no conflicts of interest.

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