title: Apoptosis induction by an analog of curcumin (BDMC-A) in human laryngeal carcinoma cells through intrinsic and extrinsic pathways.
abstract: BACKGROUND
  Head and neck cancer is the sixth most frequently occurring cancer worldwide and accounts for about 2% of all cancer-related deaths annually. Curcumin is a well-known chemopreventive agent, and apoptosis induction by curcumin has been reported in many cancer cell types. We synthesized an ortho-hydroxy substituted analog of curcumin, bisdemethoxycurcumin analog (BDMC-A), and aimed to demarcate the apoptotic effects induced by BDMC-A on human laryngeal cancer Hep-2 cells and to compare these effects with those induced by curcumin.
  
  
  METHODS
  We evaluated the apoptotic effects of BDMC-A in comparison to those of curcumin on Hep-2 cells by performing Western blotting, RT-PCR, fluorescent staining and DNA fragmentation assays. In addition, we carried out an in silico molecular docking study on the EGFR kinase domain.
  
  
  RESULTS
  We found that BDMC-A can induce apoptosis in Hep-2 cells by regulating the expression of both intrinsic and extrinsic apoptotic proteins, i.e., Bcl-2, Bax, apoptososme complex and death receptors, more efficiently than curcumin. We also observed increased nuclear fragmentation and chromatin condensation after BDMC-A treatment compared to curcumin treatment. Depolarized mitochondria and ROS generation was well pronounced in both BDMC-A and curcumin treated Hep-2 cells. Our in silico molecular docking study on the EGFR kinase domain revealed that BDMC-A may dock more efficiently than curcumin.
  
  
  CONCLUSIONS
  From our results we conclude that BDMC-A can induce apoptosis in Hep-2 laryngeal carcinoma cells more effectively than curcumin, and that this activity can be attributed to the presence of a hydroxyl group at the ortho position within this compound.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, 605014, India.
authors.forename: Kumaravel
authors.initials: K
authors.lastname: Mohankumar
authors.forename: Sankar
authors.initials: S
authors.lastname: Pajaniradje
authors.forename: Subhashree
authors.initials: S
authors.lastname: Sridharan
authors.forename: Vivek Kumar
authors.initials: VK
authors.lastname: Singh
authors.forename: Larance
authors.initials: L
authors.lastname: Ronsard
authors.forename: Akhil C
authors.initials: AC
authors.lastname: Banerjea
authors.forename: Benson Chellakkan
authors.initials: BC
authors.lastname: Selvanesan
authors.forename: Mohane Selvaraj
authors.initials: MS
authors.lastname: Coumar
authors.forename: Latha
authors.initials: L
authors.lastname: Periyasamy
authors.forename: Rukkumani
authors.initials: R
authors.lastname: Rajagopalan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D036381:Diarylheptanoids; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D036381:Diarylheptanoids; D051028:bcl-2-Associated X Protein; C034786:bisdemethoxycurcumin; D003474:Curcumin