Mechanisms Underlying the Anti-Aging and Anti-Tumor Effects of Lithocholic Bile Acid

Abstract

Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic bile acid not only causes a considerable lifespan extension in yeast, but also exhibits a substantial cytotoxic effect in cultured cancer cells derived from different tissues and organisms. The molecular and cellular mechanisms underlying the robust anti-aging and anti-tumor effects of lithocholic acid have emerged. This review summarizes the current knowledge of these mechanisms, outlines the most important unanswered questions and suggests directions for future research.

Lithocholic bile acid accumulated in yeast mitochondria orchestrates a development of an anti-aging cellular pattern by causing age-related changes in cellular proteome

“…Moreover, this study and our published data 5,36,38,[68][69][70]72 suggest the following model for how LCA-driven changes in mitochondrial proteome and functionality early and late in life of chronologically aging yeast cause a stepwise development of an anti-aging cellular pattern and its maintenance throughout lifespan (Fig. 7).…”

“…It is conceivable that such changes in expression pattern are responsible in part for the observed ability of mitochondria in yeast treated with LCA to sustain the concentration of ROS at a sublethal (hormetic) level (Fig. 7); 36,38,[68][69][70] if sustained at such level, ROS are known to promote the development and maintenance of an anti-aging cellular pattern. [3][4][5][6] By differentially altering the levels of proteins involved in the mitochondrial TCA cycle (Figs.…”

“…[3][4][5][6]16,20,25,31,33,56 Of note, we found that a treatment of yeast cells with LCA alters the agerelated chronology of these mitochondrial processes. 5,36,38,[68][69][70] We therefore hypothesized that LCA may impact not only the levels of numerous mitochondrial proteins but also the levels of proteins in cellular locations outside mitochondria. To validate our hypothesis, we used quantitative mass spectrometry to compare proteins that were recovered in total lysates of WT cells cultured in the presence of LCA or in its absence.…”

“…(Figs. 1-4) and based on the data of biochemical and cell biological analyses, 36,38,[68][69][70]72,84,85 we inferred an outline of metabolic pathways and processes that were activated (red arrows) or inhibited (green arrows) in cells cultured with exogenous LCA. Arrows next to the names of metabolites, proteins or processes denote those of them whose concentrations or efficiencies were elevated (red arrows) or reduced (green arrows) in cells cultured with exogenous LCA.…”

Investigating genetic characteristics of hepatitis B virus-associated and -non-associated hepatocellular carcinoma

“…Lithocholic acid was effective at killing several types of cancer cells, including some brain tumours and breast cancers. It is reported that lithocholic acid specifically targeted cancer cells without killing normal cells, which might improve existing chemotherapy drugs (Arlia-Ciommo et al, 2014). Findings have shown that lithocholic acid has a broad anti-tumour effect on several kinds of cancer cells derived from different tissues (Goldberg et al, 2011).…”