Cancer 2013(8)-1

 

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.

Soma Seal1 , Priyajit Chatterjee1 , Sushmita Bhattacharya1, Durba Pal1, Suman Dasgupta1,2, Rakesh Kundu1, Sandip Mukherjee1, Shelley Bhattacharya1, Mantu Bhuyan2, Pranab R. Bhattacharyya2, Gakul Baishya2, Nabin C. Barua2, Pranab K. Baruah2, Paruchuri G. Rao2, Samir Bhattacharya1,2*

1 Centre for Advanced Studies in Zoology, School of Life Science, Visva-Bharati University, Santiniketan, West Bengal, India, 2 CSIR-North East Institute of Science and Technology, Jorhat, Assam, India

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 Ser473 and Thr308; 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.

 

Supplementary

There is yet no successful chemopreventive for lung cancer, especially non small cell lung carcinoma (NSCLC), where prognosis is very poor and metastasis usually occurs prior to diagnosis. In the absence of alternative choice of therapies, such as surgical and radiotherapy, it is rather imperative to develop a powerful chemotherapy with satisfactory drug availability for this cancer. We have found that combined vapour from different oils produces two critical events; i) it inhibits cancer cell proliferation and ii) it causes death of cancer cells by inducing apoptotic pathway. Both are affected by impairing mTOR, a kinase that activates Akt which is a key kinase for regulating growth and survivability of cancer cells. Most crucial advantage here is, being vapour it could be directly delivered to lung cancer tissue by inhalation which ensures excellent drug delivery without or with marginal side effects.

 

 

Samir Bhattacharya-1

Figure summarizes the findings in this study (Seal et al., 2012. PLoS ONE 7(10): e47014)

 

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