Lithium chloride and inhibition of glycogen synthase kinase 3β as a potential therapy for serous ovarian cancer

Akiva P. Novetsky, Dominic M. Thompson, Israel Zighelboim, Premal H. Thaker, Matthew A. Powell, David G. Mutch, Paul J. Goodfellow

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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 andOVCA433, 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 1mMLiCl 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.

Original languageEnglish (US)
Pages (from-to)361-366
Number of pages6
JournalInternational Journal of Gynecological Cancer
Volume23
Issue number2
DOIs
StatePublished - Feb 2013
Externally publishedYes

Fingerprint

Lithium Chloride
Glycogen Synthase Kinase 3
Ovarian Neoplasms
Cell Line
Cytotoxins
Cell Cycle
Cell Proliferation
Therapeutics
Ascitic Fluid
Growth
Lithium
Pharmaceutical Preparations

Keywords

  • GSK3-beta
  • Lithium chloride
  • Ovarian cancer

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Novetsky, A. P., Thompson, D. M., Zighelboim, I., Thaker, P. H., Powell, M. A., Mutch, D. G., & Goodfellow, P. J. (2013). Lithium chloride and inhibition of glycogen synthase kinase 3β as a potential therapy for serous ovarian cancer. International Journal of Gynecological Cancer, 23(2), 361-366. https://doi.org/10.1097/IGC.0b013e31827cfecb

Lithium chloride and inhibition of glycogen synthase kinase 3β as a potential therapy for serous ovarian cancer. / Novetsky, Akiva P.; Thompson, Dominic M.; Zighelboim, Israel; Thaker, Premal H.; Powell, Matthew A.; Mutch, David G.; Goodfellow, Paul J.

In: International Journal of Gynecological Cancer, Vol. 23, No. 2, 02.2013, p. 361-366.

Research output: Contribution to journalArticle

Novetsky, AP, Thompson, DM, Zighelboim, I, Thaker, PH, Powell, MA, Mutch, DG & Goodfellow, PJ 2013, 'Lithium chloride and inhibition of glycogen synthase kinase 3β as a potential therapy for serous ovarian cancer', International Journal of Gynecological Cancer, vol. 23, no. 2, pp. 361-366. https://doi.org/10.1097/IGC.0b013e31827cfecb
Novetsky, Akiva P. ; Thompson, Dominic M. ; Zighelboim, Israel ; Thaker, Premal H. ; Powell, Matthew A. ; Mutch, David G. ; Goodfellow, Paul J. / Lithium chloride and inhibition of glycogen synthase kinase 3β as a potential therapy for serous ovarian cancer. In: International Journal of Gynecological Cancer. 2013 ; Vol. 23, No. 2. pp. 361-366.
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