Siphonaxanthin inhibits the growth of breast cancer cell subtypes by modulating the expression of cellular proteins associated with antioxidant defence, cell survival and apoptosis signaling.

The marine green algae, Codium species, have a long-standing history of use in Japanese and Korean food culture. Recent reports reveal that extracts/isolated compounds of Codium species exhibited immunostimulatory, anti-obese, and anticancer effects. This study aimed to delineate the molecular mechanism underlying the growth inhibitory effect of siphonaxanthin (SPX) isolated from Coduim sp. in luminal (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells. The cell viability was measured by WST-1 assay. The protein expression of the markers of antioxidant defense, cell survival, and apoptosis signaling pathways was analyzed by western blotting. The apoptosis induction by carotenoids was visualized using DAPI staining. The results showed that purified SPX inhibited the viability of MCF-7 and MDA-MB-231 cells at a concentration of 5 μM. The growth inhibitory effect of SPX was associated with suppressed protein expression of antioxidant enzyme, SOD-2, and its transcription factor, Nrf2. Carotenoid treatment subsequently blocked the expression of intracellular cell survival markers such as pAkt and pERK1/2, and a redox-sensitive transcription factor NF-kB. Further, suppression of antioxidant defence and cell survival markers was linked with apoptosis induction, with downregulated expression of Bcl-2, p-Bad, and PARP. Collectively, our results highlight a significant cancer chemopreventive role of marine carotenoid SPX in human breast cancer cells and demonstrate that it activates cell death partly through the modulation of antioxidant defense response-linked cell survival signaling markers.