Cytotoxicity of Exogenous Acetoacetate in Lithium Salt Form Is Mediated by Lithium and Not Acetoacetate

Abstract

Background/Aim: The ketogenic diet has recently gained interest as potential adjuvant therapy for cancer. Many researchers have endeavored to support this claim in vitro. One common model utilizes treatment with exogenous acetoacetate in lithium salt form (LiAcAc). We aimed to determine whether the effects of treatment with LiAcAc on cell viability, as reported in the literature, accurately reflect the influence of acetoacetate. Materials and Methods: Breast cancer and normal cell lines were treated with acetoacetate, in lithium and sodium salt forms, and cell viability was assessed. Results: The effect of LiAcAc on cells was mediated by Li ions. Our results showed that the cytotoxic effects of LiAcAc treatment were significantly similar to those caused by LiCl, and also treatment with NaAcAc did not cause any significant cytotoxic effect. Conclusion: Treatment of cells with LiAcAc is not a convincing in vitro model for studying ketogenic diet. These findings are highly important for interpreting previously published results, and for designing new experiments to study the ketogenic diet in vitro.

Poly-Unsaturated Fatty Acids (PUFAs) from Cunninghamella elegans Grown on Glycerol Induce Cell Death and Increase Intracellular Reactive Oxygen Species

“…Synergistic actions were documented; however, the IC 50 exhibited by LiCl alone was measured to be around 20 mM after 48 h of exposure [71]. Other groups, mainly focusing on hepatocellular carcinoma and breast cancer, came up with similar results [72][73][74][75][76][77]. Another study, testing LiCl, documented the suppression of the proliferation in the ameloblastoma cell line AM-1, using a dose of 1 mM [78].…”

Metabolic alterations and cellular responses to β-Hydroxybutyrate treatment in breast cancer cells

“…Some studies demonstrate that treatment with AcA reduced cell growth [ 11 ], and viability [ 12 ], decreased ATP production [ 13 ], increased apoptosis in cancer cells [ 12 ], induced oxidative stress [ 14 ], diminished cancer cachexia, and altered metabolic profile [ 15 ]. Though some in vitro studies may be plagued by technical issues [ 16 ]. The more prevalent KB, βHb [ 17 ], in turn, delivers controversial results [ 18 ].…”

Ketone Bodies Induce Unique Inhibition of Tumor Cell Proliferation and Enhance the Efficacy of Anti-Cancer Agents

“…Lithium salt is the commercially available form of acetoacetate, but it is known that lithium ions alone are capable of inhibiting proliferation of some cancer cells [ 10 ]. The effect of non-keto acid salts, such as lithium chloride, on cancer cell proliferation have been investigated [ 11 , 12 ]. Lithium chloride was found to reproduce the effect of lithium acetoacetate on an equimolar basis (at concentrations of 10–15 mM) on a number of different human cancer cell lines [ 11 , 12 ].…”

“…The effect of non-keto acid salts, such as lithium chloride, on cancer cell proliferation have been investigated [ 11 , 12 ]. Lithium chloride was found to reproduce the effect of lithium acetoacetate on an equimolar basis (at concentrations of 10–15 mM) on a number of different human cancer cell lines [ 11 , 12 ]. These included human breast cancer cell lines (MCF-7, MDA-MB-231 and Hs578T), SV40-large T antigen-immortalized non-transformed mammary luminal epithelial cells (HB2) and a normal human fibroblast cell line (HSF064) [ 1 ].…”

“…These included human breast cancer cell lines (MCF-7, MDA-MB-231 and Hs578T), SV40-large T antigen-immortalized non-transformed mammary luminal epithelial cells (HB2) and a normal human fibroblast cell line (HSF064) [ 1 ]. Of note, both agents were found to inhibit the viability of the two untransformed cell lines’ (HB2 and HSF064) growth to about the same extent as they did for the cancer cells [ 11 ]. Similar results were found in a study of neuroblastoma and renal cell carcinoma cell lines and two untransformed cell lines [ 2 ].…”