Kavalappa Yogendra Prasad, Stephen Nimish Mol, Baskaran Jayalakshmi Kirubakaran, Sugawara Tatsuya, Manabe Yuki, Hirata Takashi, Ponesakki Ganesan
Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute (CFTRI), Mysuru, 570 020, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India.
Med Oncol. 2025 Jun 14;42(7):259. doi: 10.1007/s12032-025-02798-y.
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.
海洋绿藻，松藻属，在日本和韩国的饮食文化中有着悠久的使用历史。最近的报道显示，松藻属的提取物/分离化合物具有免疫刺激、抗肥胖和抗癌作用。本研究旨在阐明从松藻属分离出的虹吸叶黄素（SPX）对管腔型（MCF-7）和三阴性（MDA-MB-231）乳腺癌细胞生长抑制作用的分子机制。通过WST-1法测定细胞活力。通过蛋白质印迹分析抗氧化防御、细胞存活和凋亡信号通路标志物的蛋白质表达。使用DAPI染色观察类胡萝卜素诱导的细胞凋亡。结果表明，纯化的SPX在浓度为5μM时可抑制MCF-7和MDA-MB-231细胞的活力。SPX的生长抑制作用与抗氧化酶SOD-2及其转录因子Nrf2的蛋白质表达受抑制有关。类胡萝卜素处理随后阻断了细胞内细胞存活标志物如pAkt和pERK1/2以及氧化还原敏感转录因子NF-κB的表达。此外，抗氧化防御和细胞存活标志物的抑制与细胞凋亡诱导有关，Bcl-2、p-Bad和PARP的表达下调。总的来说，我们的结果突出了海洋类胡萝卜素SPX在人乳腺癌细胞中的显著癌症化学预防作用，并表明它部分通过调节与抗氧化防御反应相关的细胞存活信号标志物来激活细胞死亡。
