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 viabil-
ity 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.