Vapor of volatile oils from Litsea cubeba seed induces apoptosis and causes cell cycle arrest in lung cancer cells

PLoS One. 2012;7(10):e47014. doi: 10.1371/journal.pone.0047014. Epub 2012 Oct 16.

Abstract

Non-small cell lung carcinoma (NSCLC) is a major killer in cancer related human death. Its therapeutic intervention requires superior efficient molecule(s) as it often becomes resistant to present chemotherapy options. Here we report that vapor of volatile oil compounds obtained from Litsea cubeba seeds killed human NSCLC cells, A549, through the induction of apoptosis and cell cycle arrest. Vapor generated from the combined oils (VCO) deactivated Akt, a key player in cancer cell survival and proliferation. Interestingly VCO dephosphorylated Akt at both Ser(473) and Thr(308); through the suppression of mTOR and pPDK1 respectively. As a consequence of this, diminished phosphorylation of Bad occurred along with the decreased Bcl-xL expression. This subsequently enhanced Bax levels permitting the release of mitochondrial cytochrome c into the cytosol which concomitantly activated caspase 9 and caspase 3 resulting apoptotic cell death. Impairment of Akt activation by VCO also deactivated Mdm2 that effected overexpression of p53 which in turn upregulated p21 expression. This causes enhanced p21 binding to cyclin D1 that halted G1 to S phase progression. Taken together, VCO produces two prong effects on lung cancer cells, it induces apoptosis and blocked cancer cell proliferation, both occurred due to the deactivation of Akt. In addition, it has another crucial advantage: VCO could be directly delivered to lung cancer tissue through inhalation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Caspases / metabolism
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclin D1 / metabolism
  • Humans
  • Litsea / chemistry*
  • Lung Neoplasms / metabolism
  • Oils, Volatile / isolation & purification
  • Oils, Volatile / pharmacology*
  • Phosphorylation / drug effects
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plant Oils / isolation & purification
  • Plant Oils / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Seeds / chemistry*
  • Signal Transduction / drug effects

Substances

  • Oils, Volatile
  • Plant Extracts
  • Plant Oils
  • Cyclin D1
  • Proto-Oncogene Proteins c-akt
  • Caspases

Grant support

This research work was financially supported by the grant from CSIR-NEEP Project (HCP-005). The authors SS and PC are thankful to the Department of Science & Technology, Govt. of India, New Delhi; Sushmita Bhattacharya, DP and RK are indebted to Council of Scientific and Industrial Research (CSIR), New Delhi, for the award of Research Fellowships. SD is thankful to UGC for Dr. D. S. Kothari PDF & CSIR-NEIST for QHF; and Samir Bhattacharya to the Indian National Science Academy for his INSA Senior Scientist position. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.