Lithium modulates cancer cell growth, apoptosis, gene expression and cytokine production in HL-60 promyelocytic leukaemia cells and their drug-resistant sub-clones

Biological Trace Element Research
Thabe MatsebatlelaRolf Becker

Abstract

Lithium has been an FDA-approved and preferred drug for the treatment of mood disorders for many years, and cumulative evidence has pointed towards its potential use as an anti-cancer agent. Previous studies in our laboratory have demonstrated that lithium induces apoptotic cell death in HL-60 promyelocytes at concentrations of 10 mM and above. A lithium-tolerant HL-60 sub-clone, resistant to up to 15 mM lithium, was also generated and its growth profile reported. Treatment of cells with lithium resulted in a dose-dependent induction of p53, retinoblastoma (Rb) and bax expression which was accompanied by concomitant inhibition of bcl-2 expression as demonstrated using immunohistochemical microscopy. These results seem to suggest that lithium induced cell death in these cells by inhibiting expression of anti-apoptotic protein, bcl-2, while inducing higher expression of its pro-apoptotic counterparts which include bax. Expression of bax and bcl-2 is also linked to expression of inflammation-regulating cytokines. Using ELISA assays, lithium was demonstrated to induce production of pro-inflammatory cytokines, IL-6 and TNF-α, while inhibiting release of anti-inflammation-related IL-2 and IL-10 in a dose-dependent fashion. Our findin...Continue Reading

References

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Citations

Feb 5, 2013·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Yan LanZi-Chun Hua
Mar 5, 2014·Human Psychopharmacology·Shinya WatanabeTetsuro Ohmori
May 8, 2014·ACS Chemical Neuroscience·Ahmad Nassar, Abed N Azab
May 12, 2016·Bulletin of Experimental Biology and Medicine·A P LykovV I Konenkov
Jan 30, 2020·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Dena A-E MohammedR G Ahmed
Aug 11, 2020·International Journal of Inflammation·Raymond T MakolaThabe M Matsebatlela

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