Fucoxanthin induces apoptosis in human glioma cells. - GreenMedInfo Summary
Fucoxanthin induces apoptosis in human glioma cells by triggering ROS-mediated oxidative damage and regulating MAPKs and PI3K/AKT pathways.
J Agric Food Chem. 2019 Jan 28. Epub 2019 Jan 28. PMID: 30688446
Fucoxanthin a natural carotenoid derived from algae exhibits novel anticancer potential. However, fucoxanthin with high purity was hard to prepare and the anticancer mechanism remains elusive. In the present study, fucoxanthin with high purity was prepared and purified from marine micralgae Nitzschia sp. by silica gel column chromatography (SGCC), and the underlying mechanism against human giloma cells was evaluated. The results showed that fucoxanthin time- and dose-dependently inhibited U251 human glioma cells growth by induction of apoptosis (64.4±4.8, P<0.01), accompanied by PARP cleavage and caspases 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 convinced 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. Addition of kinase inhibitors further confirmed the importance of MAPKs and PI3K/AKT pathways in fucoxanthin-induced cells growth inhibition (32.5±3.6, P<0.01). However, ROS inhibition by 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 ROS as early apoptotic event involved in fucoxanthin-mediated anticancer mechanism. Taken together, these results suggested that fucoxanthin induced U251 human glioma cells apoptosis by triggering ROS-mediated oxidative damage and dysfunction of MAPKs and PI3K/AKT pathways, which validated that fucoxanthin may be candidates with potential application in cancer chemotherapy and chemoprevention.