title: A novel derivative of riccardin D induces cell death through lysosomal rupture in vitro and inhibits tumor growth in vivo.
abstract: In the present study, the effect of a novel derivative of riccardin D (RD-N) against cancer cell lines was investigated in vitro and in vivo. We found that RD-N accumulated in the lysosomes associated with lysosomal swelling. As a result, the destabilized lysosomes induced cathepsins to release from the lysosomes into the cytosol and induced cell death which displayed features characteristic to both apoptosis and necrosis. In vivo tumor xenograft model indicated treatment of RD-N significantly reduced size and weight of the tumor compared with vehicles. These findings suggest RD-N could be a promising candidate for treatment of cancer.
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of MOE (Ministry of Education), Shandong University, Jinan 250012, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Lining
authors.initials: L
authors.lastname: Wang
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Hu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ji
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Lin
authors.forename: Huiqing
authors.initials: H
authors.lastname: Yuan
authors.forename: Mei
authors.initials: M
authors.lastname: Ji
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Lou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009336:Necrosis; D010647:Phenyl Ethers / Q000378:metabolism / Q000494:pharmacology*; D013267:Stilbenes / Q000378:metabolism / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003598:Cytoskeletal Proteins; D010647:Phenyl Ethers; D013267:Stilbenes; C578790:riccardin D-N; D005047:Etoposide