Antineoplastic potential of Kushneria avicenniae pigments via modulation of the BAX/BCL-2 axis and CASP-9 pathway in inducing G2/M arrest and apoptosis in liver and breast cancer.

Since cancer continues to be a chief cause of disease and mortality worldwide, new and efficient treatment approaches are desperately needed. Natural substances have become a foremost source of bioactive molecules with intriguing cytotoxic effects, particularly those originating from microbes. The cytotoxic potential of pigments derived from the halophilic bacteria Kushneria avicenniae HA346018, which was isolated from mangrove environments, is investigated in this work. These pigments' cytotoxic, apoptotic, and cell cycle-modulating properties were assessed in human HepG2 and MCF-7 cell lines. Both cancer cell lines revealed a dose-dependent decrease in cell viability, indicating the pigment extract's potent cytotoxic effects in vitro. HepG2 and MCF-7 cells have computed IC50 values of 52.7 ± 3.8 µg/mL and 48.3 ± 4.1 µg/mL, respectively. Its notable selective cytotoxicity highlighted the pigment's potential as a targeted therapy, which revealed much less toxicity against normal WI-38 cells. A notable concentration of cells in the G2/M phase and a considerable change in cell cycle progression were seen by flow cytometric analysis, indicating the extract's potential to cause cell cycle arrest. The regulation of cyclin-dependent kinases (CDKs) and DNA damage response pathways was associated with this inhibition at the G2/M checkpoint. Moreover, Annexin V-FITC/PI labeling and subsequent flow cytometric analysis verified that the pigment caused both early and late apoptotic events. The mitochondrial mechanisms that mediated the apoptosis were the elevation of pro-apoptotic proteins like Bax and the downregulation of anti-apoptotic proteins like Bcl-2, which eventually led to caspase activation. These results establish Kushneria avicenniae pigments as a viable source of bioactive chemicals with therapeutic potential for breast and liver malignancies by offering new mechanistic insights into their apoptosis-inducing effect in cancer cell lines. This study encourages more investigation into natural compounds obtained from microorganisms as potential substitutes for traditional cancer therapies.