Bufalin enhances TRAIL-induced apoptosis by redistributing death receptors in lipid rafts in breast cancer cells.
Studies have shown that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells. However, breast cancer cells are generally resistant to TRAIL. In the present study, we explored the effect of bufalin on TRAIL-induced breast cancer cell apoptosis. The results showed that bufalin enhanced TRAIL-induced apoptosis in MCF-7 and MDA-MB-231 breast cancer cells by activating the extrinsic apoptotic pathway. Bufalin also promoted the clustering of death receptor 4 (DR4) and DR5 in aggregated lipid rafts. The cholesterol-sequestering agent methyl-β-cyclodextrin reversed the DR4 and DR5 clustering and reduced bufalin+TRAIL-induced apoptosis. Overall, these results indicate that bufalin enhanced TRAIL-induced apoptosis in breast cancer cells by the partial redistribution of DRs in lipid rafts.
aDepartment of Medical Oncology, The First Hospital of China Medical University bDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, China.
Shunchao
S
Yan
Xiujuan
X
Qu
Ling
L
Xu
Xiaofang
X
Che
Yanju
Y
Ma
Lingyun
L
Zhang
Yuee
Y
Teng
Huawei
H
Zou
Yunpeng
Y
Liu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002018:Bufanolides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D047392:beta-Cyclodextrins / Q000494:pharmacology
D000970:Antineoplastic Agents; D002018:Bufanolides; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol; C022777:bufalin