Induction of apoptosis and autophagic cell death by the vanillin derivative 6-bromine-5-hydroxy-4-methoxybenzaldehyde is accompanied by the cleavage of DNA-PKcs and rapid destruction of c-Myc oncoprotein in HepG2 cells.
Autophagy is a regulated lysosomal pathway involving the bulk degradation of cytoplasmic contents, and is an emerging attractive therapeutic approach for treating cancers. In the present study, we demonstrates that bromovanin (6-bromine-5-hydroxy-4-methoxybenzaldehyde), a vanillin derivative, exhibits a potent antiproliferative effect on a broad spectrum of cancer cell lines, but it induces apoptosis with a large variation in extent on different cancer cell lines. Ultrastructural observation in transmission electron microscopy reveals that autophagy is another type of cell death induced by bromovanin in HepG2 cells. Treatment with bromovanin significantly increases cellular ROS level as well as elicits DNA double-strand breaks as indicated by comet assay and the increased phosphorylated H2AX. Cleavage and inactivation of DNA-PKcs induced by bromovanin is found to occur concurrently with a rapid destruction of c-Myc oncoprotein. These multiple effects of bromovanin, especially the induction of both apoptosis and autophagy, make it very appealing for the development as a novel anticancer drug.
Yan
Yu-Qian
YQ
Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, PR China.
Zhang
Bo
B
Wang
Lin
L
Xie
Yue-Hua
YH
Peng
Tao
T
Bai
Bei
B
Zhou
Ping-Kun
PK
D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001547:Benzaldehydes / Q000494:pharmacology*; D045744:Cell Line, Tumor; D020552:Comet Assay; D004249:DNA Damage; D051747:DNA-Activated Protein Kinase / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D046529:Microscopy, Electron, Transmission; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D017382:Reactive Oxygen Species
D001547:Benzaldehydes; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species; C515564:bromovanin; D051747:DNA-Activated Protein Kinase