title: Curcumin induces p53-independent necrosis in H1299 cells via a mitochondria-associated pathway.
abstract: Curcumin has been shown to have various therapeutic and/or adjuvant therapeutic effects on human cancers, as it inhibits cancer cell proliferation and induces apoptosis through p53-dependent molecular pathways. However, numerous cancer cell types bear a mutant p53 gene, and whether curcumin has any therapeutic effects on p53-deficient/mutant cancer cells has remained elusive. The present study sought to determine whether curcumin exerts any anti-proliferative and cytotoxic effects on the p53-deficient H1299 human lung cancer cell line via a p53-independent mechanism. An MTT assay and flow cytometric analysis indicated that curcumin significantly decreased cell proliferation and induced necrotic cell death. Western blot analysis of the cytosolic and mitochondrial fractions of H1299 cells as well as a fluorometric caspase assay indicated that curcumin-induced necrosis was mitochondria- and caspase-dependent, and resulted in cytochrome c release. Of note, this necrotic cell death was reduced following inhibition of B-cell lymphoma‑2 (Bcl-2)‑associated X protein (Bax) or Bcl‑2 homologous antagonist killer (Bak) as well as overexpression of Bcl-2. In conclusion, the present study suggested that curcumin-induced necrotic cell death was mediated via a p53-independent molecular pathway, which was associated with Bax and Bak translocation, caspase activation and cytochrome c release.
authors.affiliation: Department of Pharmacy, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Feie
authors.initials: F
authors.lastname: Li
authors.affiliation: School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D020169:Caspases; D003474:Curcumin