title: Anti-lung cancer potential of pure esteric-glycoside condurangogenin A against nonsmall-cell lung cancer cells in vitro via p21/p53 mediated cell cycle modulation and DNA damage-induced apoptosis.
abstract: BACKGROUND
  Marsdenia condurango (condurango) is a tropical woody vine native to South America. Our earlier study was limited to evaluation of anti-cancer potentials of crude condurango extract and its glycoside-rich components in vitro on lung cancer.
  
  
  OBJECTIVE
  This study aims at evaluating the effect of the single isolated active ingredient condurangogenin A (ConA; C32H42O7) on A549, H522 and H460-nonsmall-cell lung cancer cells.
  
  
  METHODS
  ConA was isolated by column chromatography and analyzed by mass spectroscopy, Fourier transform infrared spectroscopy and proton-nuclear magnetic resonance. diphenyltetrazolium bromide assays were conducted on three cell-types using 6%-alcohol as control. Critical studies on cellular morphology, cell-cycle regulation, reactive oxygen species, mitochondrial membrane potential, and DNA-damage were made, and expressions of related signaling markers studied.
  
  
  RESULTS
  As IC50 doses of ConA proved to be too high and toxic to both A549 and H522 cells, all experimental studies were carried out on H460 cells with the IC50 dose (32 μg/ml - 24 h). Cellular morphology revealed typical apoptotic features after ConA treatment. At early treatment hours (2 h-12 h), maximum cells were arrested at G0/G1 phase that could be correlated with reduced level of cyclin D1-CDK with p21 up-regulation. At 18 h - 24 h, sub G0/G1 cell population was increased gradually, as revealed from cytochrome-c release and caspase-3 activation, further confirming the apoptosis-inducing ability of ConA at later phases. Gradual increase of TUNEL-positive cells with significant modulation of mitochondria-dependent apoptotic markers at longer time-points would establish apoptosis-induction property of ConA, indicating its potential as a strong candidate for anti-cancer drug formulation.
  
  
  CONCLUSIONS
  Further studies are warranted against other types of cancer cells and animal models before its possible human use.
authors.affiliation: Department of Zoology, Cytogenetics and Molecular Biology Laboratory, University of Kalyani, Kalyani, West Bengal, India.
authors.forename: Sourav
authors.initials: S
authors.lastname: Sikdar
authors.affiliation: Department of Zoology, Cytogenetics and Molecular Biology Laboratory, University of Kalyani, Kalyani, West Bengal, India.
authors.forename: Avinaba
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Department of Zoology, Cytogenetics and Molecular Biology Laboratory, University of Kalyani, Kalyani, West Bengal, India.
authors.forename: Anisur Rahman
authors.initials: AR
authors.lastname: Khuda-Bukhsh
keywords: Apoptosis; H460-nonsmall cell lung cancer cell; cell cycle; condurangogenin A; cyclin D1-CDK pathway; p21/p53