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Induction of Apoptosis in Human Glioma Cells by Fucoxanthin via Triggering of ROS-Mediated Oxidative Damage and Regulation of MAPKs and PI3K-AKT Pathways
Wu, Hua-lian; Fu, Xiao-yan; Cao, Wen-giang; Xiang, Wen-zhou; Hou, Ya-jun; Ma, Jin-kui; Wang, Ying; Fan, Cun-dong
2019
Source PublicationJOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
ISSN0021-8561
Volume67Issue:8Pages:2212
AbstractFucoxanthin, 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 (SGCC), 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 (64.4 +/- 4.8, P < 0.01) accompanied by PARP cleavage and caspase activation (244 +/- 14.2, P < 0.01). Mechanically, fucoxanthin time-dependently triggered reactive-oxygen-species (ROS)-mediated DNA damage (100 +/- 7.38, P < 0.01), 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 (32.5 +/- 3.6, P < 0.01). However, ROS inhibition by the antioxidant glutathione (GSH) effectively inhibited fucoxanthin-induced DNA damage, attenuated the dysfunction of MAPKs and PI3K-AKT pathways, and eventually blocked fucoxanthin-induced cytotoxicity (54.3 +/- 5.6, P < 0.05) and cell apoptosis (32.7 +/- 2.5, P < 0.05), 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.
DepartmentLMB
Keywordfucoxanthin glioma cells reactive oxygen species apoptosis oxidative damage
DOI10.1021/acs.jafc.8b07126
Citation statistics
Cited Times:10[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.scsio.ac.cn/handle/344004/17896
Collection中科院海洋生物资源可持续利用重点实验室
Affiliation1.[Wu, Hua-lian
2.Chinese Acad Sci, CAS Key Lab Trop Marine Bioresources & Ecol LMB C, Guangdong Key Lab Marine Mat Med LMMM GD, South China Sea Inst Oceanol, Guangzhou 510301, Guangdong, Peoples R China
3.[Fu, Xiao-yan
4.Hou, Ya-jun
5.Wang, Ying
6.Taishan Med Univ, Key Lab Cerebral Microcirculat Univ Shandong, Tai An 271000, Shandong, Peoples R China
7.Zhuhai Hopegenes Med & Phamaceut Inst, Hengqin New Area, Zhuhai 519000, Guangdong, Peoples R China
8.Zhaoqing Univ, Sch Food & Pharmaceut Engn, Zhaoqing 526061, Guangdong, Peoples R China
Recommended Citation
GB/T 7714
Wu, Hua-lian,Fu, Xiao-yan,Cao, Wen-giang,et al. Induction of Apoptosis in Human Glioma Cells by Fucoxanthin via Triggering of ROS-Mediated Oxidative Damage and Regulation of MAPKs and PI3K-AKT Pathways[J]. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,2019,67(8):2212, 2219.
APA Wu, Hua-lian.,Fu, Xiao-yan.,Cao, Wen-giang.,Xiang, Wen-zhou.,Hou, Ya-jun.,...&Fan, Cun-dong.(2019).Induction of Apoptosis in Human Glioma Cells by Fucoxanthin via Triggering of ROS-Mediated Oxidative Damage and Regulation of MAPKs and PI3K-AKT Pathways.JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY,67(8),2212.
MLA Wu, Hua-lian,et al."Induction of Apoptosis in Human Glioma Cells by Fucoxanthin via Triggering of ROS-Mediated Oxidative Damage and Regulation of MAPKs and PI3K-AKT Pathways".JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 67.8(2019):2212.
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