title: Vapor of volatile oils from Litsea cubeba seed induces apoptosis and causes cell cycle arrest in lung cancer cells.
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.
authors.affiliation: Centre for Advanced Studies in Zoology, School of Life Science, Visva-Bharati University, Santiniketan, West Bengal, India.
authors.forename: Soma
authors.initials: S
authors.lastname: Seal
authors.forename: Priyajit
authors.initials: P
authors.lastname: Chatterjee
authors.forename: Sushmita
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Durba
authors.initials: D
authors.lastname: Pal
authors.forename: Suman
authors.initials: S
authors.lastname: Dasgupta
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kundu
authors.forename: Sandip
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Shelley
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Mantu
authors.initials: M
authors.lastname: Bhuyan
authors.forename: Pranab R
authors.initials: PR
authors.lastname: Bhattacharyya
authors.forename: Gakul
authors.initials: G
authors.lastname: Baishya
authors.forename: Nabin C
authors.initials: NC
authors.lastname: Barua
authors.forename: Pranab K
authors.initials: PK
authors.lastname: Baruah
authors.forename: Paruchuri G
authors.initials: PG
authors.lastname: Rao
authors.forename: Samir
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D006801:Humans; D032862:Litsea / Q000737:chemistry*; D008175:Lung Neoplasms / Q000378:metabolism; D009822:Oils, Volatile / Q000302:isolation & purification / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D010938:Plant Oils / Q000302:isolation & purification / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012639:Seeds / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009822:Oils, Volatile; D010936:Plant Extracts; D010938:Plant Oils; D019938:Cyclin D1; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases