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作者

Hua-Lian Wu Xiao-Yan Fu Wen-Qiang Cao Wen-Zhou Xiang Ya-Jun Hou Jin-Kui Ma Ying Wang Cun-Dong Fan

作者单位

Pharmaceutical Engineering , Zhaoqing University , Zhaoqing , Guangdong 526061 , China. CAS Key Laboratory of Tropical Marine Bio-resources and Ecology (LMB-CAS), Guangdong Key Laboratory of Marine Materia Medica (LMMM-GD), South China Sea Institute of Oceanology , Chinese Academy of Sciences , Guangzhou , Guangdong 510301 , China. Key Lab of Cerebral Microcirculation in Universities of Shandong , Taishan Medical University , Taian , Shandong 271000 , China. Zhuhai Hopegenes Medical & Phamaceutical Institute , Hengqin New Area, Zhuhai , Guangdong 519000 , China. School of Food & amp

刊名

Journal of agricultural and food chemistry

年份

2019

卷号

Vol.67 No.8

页码

2212-2219

ISSN

1520-5118

关键词

apoptosis fucoxanthin glioma cells oxidative damage reactive oxygen species

摘要

Fucoxanthin, a natural carotenoid derived from algae, exhibits novel anticancer potential. However, fucoxanthin with high purity is hard to prepare, and the anticancer mechanism remains elusive. In the present study, fucoxanthin with high purity was prepared and purified from the marine microalgae Nitzschia sp. by silica-gel column chromatography , and the underlying mechanism against human glioma cells was evaluated. The results showed that fucoxanthin time- and dose-dependently inhibited U251-...更多

Fucoxanthin, a natural carotenoid derived from algae, exhibits novel anticancer potential. However, fucoxanthin with high purity is hard to prepare, and the anticancer mechanism remains elusive. In the present study, fucoxanthin with high purity was prepared and purified from the marine microalgae Nitzschia sp. by silica-gel column chromatography , and the underlying mechanism against human glioma cells was evaluated. The results showed that fucoxanthin time- and dose-dependently inhibited U251-human-glioma-cell growth by induction of apoptosis accompanied by PARP cleavage and caspase activation . Mechanically, fucoxanthin time-dependently triggered reactive-oxygen-species -mediated DNA damage , as evidenced by the phosphorylation activation of Ser1981-ATM, Ser428-ATR, Ser15-p53, and Ser139-histone. Moreover, fucoxanthin treatment also time-dependently caused dysfunction of MAPKs and PI3K-AKT pathways, as demonstrated by the phosphorylation activation of Thr183-JNK, Thr180-p38, and Thr202-ERK and the phosphorylation inactivation of Ser473-AKT. The addition of kinase inhibitors further confirmed the importance of MAPKs and PI3K-AKT pathways in fucoxanthin-induced cell-growth inhibition . However, ROS inhibition by the antioxidant glutathione effectively inhibited fucoxanthin-induced DNA damage, attenuated the dysfunction of MAPKs and PI3K-AKT pathways, and eventually blocked fucoxanthin-induced cytotoxicity and cell apoptosis , indicating that ROS production, an early apoptotic event, is involved in the fucoxanthin-mediated anticancer mechanism. Taken together, these results suggested that fucoxanthin induced U251-human-glioma-cell apoptosis by triggering ROS-mediated oxidative damage and dysfunction of MAPKs and PI3K-AKT pathways, which validated that fucoxanthin may be a candidate for potential applications in cancer chemotherapy and chemoprevention.收起

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