Curcumin induces apoptosis of upper aerodigestive tract cancer cells by targeting multiple pathways

• Published in: PloS one Vol. 10; no. 4; p. e0124218
• Main Authors: Amin, A R M Ruhul, Haque, Abedul, Rahman, Mohammad Aminur, Chen, Zhuo Georgia, Khuri, Fadlo Raja, Shin, Dong Moon
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.04.2015; Public Library of Science (PLoS)
• Subjects: Ablation; AKT protein; Anticancer properties; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Bcl-2 protein; Biotechnology; Cancer; Cancer prevention; Cancer therapies; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemotherapy; Clinical trials; Curcumin; Curcumin - pharmacology; Deactivation; Digestive System Neoplasms - metabolism; Digestive System Neoplasms - pathology; DNA-Binding Proteins - metabolism; Dose-Response Relationship, Drug; Head & neck cancer; Head and neck cancer; Health aspects; Hematology; Humans; Inactivation; Inhibition; Inhibitory Concentration 50; Kinases; Lung cancer; Lung diseases; Mitochondria - drug effects; Mitochondria - metabolism; Molecular modelling; Nuclear Proteins - metabolism; Oncology; p53 Protein; Pathways; Powder; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Signal transduction; Signal Transduction - drug effects; Tumor cell lines; Tumor Protein p73; Tumor proteins; Tumor suppressor genes; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins - metabolism; Tumors; Atlanta Georgia; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0124218

Curcumin, a natural compound isolated from the Indian spice "Haldi" or "curry powder", has been used for centuries as a traditional remedy for many ailments. Recently, the potential use of curcumin in cancer prevention and therapy urges studies to uncover the molecular mechanisms associated with its anti-tumor effects. In the current manuscript, we investigated the mechanism of curcumin-induced apoptosis in upper aerodigestive tract cancer cell lines and showed that curcumin-induced apoptosis is mediated by the modulation of multiple pathways such as induction of p73, and inhibition of p-AKT and Bcl-2. Treatment of cells with curcumin induced both p53 and the related protein p73 in head and neck and lung cancer cell lines. Inactivation of p73 by dominant negative p73 significantly protected cells from curcumin-induced apoptosis, whereas ablation of p53 by shRNA had no effect. Curcumin treatment also strongly inhibited p-AKT and Bcl-2 and overexpression of constitutively active AKT or Bcl-2 significantly inhibited curcumin-induced apoptosis. Taken together, our findings suggest that curcumin-induced apoptosis is mediated via activating tumor suppressor p73 and inhibiting p-AKT and Bcl-2.