Pro-apoptotic and cell cycle-modulating effects of lobaric and rhizocarpic acids in human leukemic cell lines

Abstract

Background Lobaric and rhizocarpic acids are secondary metabolites isolated from Antarctic lichens. While several biological activities have been described for lobaric acid, the cellular effects of rhizocarpic acid remain poorly characterized. This study investigated the impact of these compounds on proliferation, apoptosis, and cell cycle regulation in human leukemic cell models. Methods and Results Human leukemic K562 and MOLM-6 cells were exposed to lobaric and rhizocarpic acids under defined experimental conditions; cell viability, apoptosis, cell cycle distribution, and protein expression were evaluated using cell proliferation assays, flow cytometry, and western blot analysis. Both metabolites reduced cell growth and promoted caspase-dependent apoptosis in K562 and MOLM-6 cells. At the molecular level, in K562 cells, lobaric acid treatment was associated with increased Bax protein expression, whereas rhizocarpic acid induced upregulation of Bcl-2. In MOLM-6 cells, both compounds decreased STAT5 protein expression. In addition, both metabolites altered cell cycle distribution. Lobaric acid caused a significant increase of K562 cells in the G 2 /M phase and a transient rise of MOLM-6 cells in G 1 phase, whereas rhizocarpic acid increased the proportion of cells in the G 1 phase, with a concomitant reduction in S and G 2 /M populations in both leukemic cell lines. Analysis of cell cycle regulatory protein expression showed modulation of cyclin B1, cyclin D3, CDK4, and CDK6 by rhizocarpic acid, and upregulation of cyclin D3 by lobaric acid in both cell lines. Conclusions Overall, these findings provide new insights into the molecular mechanisms underlying the bioactivity of lichen-derived metabolites in leukemic cells and identify rhizocarpic acid as a previously uncharacterized modulator of apoptosis- and cell cycle-related pathway progression. Further studies, including comprehensive dose-response analyses and in vivo evaluations, will be necessary to fully define their therapeutic potential.

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