title: Diarylheptanoid-myricanone isolated from ethanolic extract of Myrica cerifera shows anticancer effects on HeLa and PC3 cell lines: signalling pathway and drug-DNA interaction.
abstract: OBJECTIVE
  To test if myricanone (C21H24O5), a cyclic diarylheptanoid, has anticancer effects on two different cancer cell lines HeLa and PC3. The present study was conducted with a note on the drug-DNA interaction and apoptotic signalling pathway.
  
  
  METHODS
  Several studies like cytotoxicity, nuclear damage, annexin-V-fluorescein isothiocyanate (FITC)/propidium iodide (PI)-labelled apoptotic assay and cell cycle arrest, immunoblot and reverse transcriptase-polymerase chain reaction (RT-PCR) were used following standard protocols. Circular dichroism (CD) spectroscopy was also done to evaluate whether myricanone effectively interacted with DNA to bring about conformational changes that could strongly inhibit the cancer cell proliferation.
  
  
  RESULTS
  Myricanone showed a greater cytotoxic effect on PC3 cells than on HeLa cells. Myricanone promoted G0/G1 arrest in HeLa cells and S phase arrest in PC3 cells. Nuclear condensation and annexin V-FITC/PI studies revealed that myricanone promoted apoptotic cell death. CD spectroscopic data indicated that myricanone had an interaction with calf thymus DNA that changed DNA structural conformation. RT-PCR and immunoblot studies revealed that myricanone activated the apoptotic signalling cascades through down-regulation of transcription factors like nuclear factor-κB (NF-κB) (p65), and signal transducers and activators of transcription 3 (STAT3); cell cycle regulators like cyclin D1, and survivin and other signal proteins like Bcl-2 and up-regulation of Bax, caspase-9 and caspase-3.
  
  
  CONCLUSIONS
  Myricanone induced apoptosis in both types of cancer cells by triggering caspase activation, and suppression of cell proliferation by down-regulation of NF-κB and STAT3 signalling cascades, which makes it a suitable candidate for possible use in the formulation of therapeutic agent for combating cancer.
authors.affiliation: Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani-741235, India; E-mail: prof_arkb@yahoo.co.in; khudabukhsh_48@rediffmail.com.
authors.forename: Avijit
authors.initials: A
authors.lastname: Paul
authors.forename: Sreemanti
authors.initials: S
authors.lastname: Das
authors.forename: Jayeeta
authors.initials: J
authors.lastname: Das
authors.forename: Asmita
authors.initials: A
authors.lastname: Samadder
authors.forename: Kausik
authors.initials: K
authors.lastname: Bishayee
authors.forename: Ratan
authors.initials: R
authors.lastname: Sadhukhan
authors.forename: Anisur Rahman
authors.initials: AR
authors.lastname: Khuda-Bukhsh
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000378:metabolism*; D036381:Diarylheptanoids / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D031641:Myrica / Q000737:chemistry*; D010936:Plant Extracts / Q000032:analysis*; D015398:Signal Transduction; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D036381:Diarylheptanoids; D010936:Plant Extracts; C041795:myricanone; D004247:DNA