caa a22 4500 606234586 CHVBK 20210128101238.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s11010-015-2406-2 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2406-2 A carbazole alkaloid deactivates mTOR through the suppression of rictor and that induces apoptosis in lung cancer cells [Elektronische Daten] [Priyajit Chatterjee, Soma Seal, Sandip Mukherjee, Rakesh Kundu, Mantu Bhuyan, Nabin Barua, Pranab Baruah, Santi Babu, Samir Bhattacharya] Non-small cell lung cancer (NSCLC) is known to be a difficult cancer to treat because of its poor prognosis, limited option for surgery, and resistance to chemo or radiotherapy. In this study, we have demonstrated that suppression of rictor expression in A549 and H1299 NSCLC cells by mahanine, a carbazole alkaloid, disrupted constitutive activation of mTOR and Akt. Mahanine suppression of rictor gene expression and consequent attenuation of its protein expression affected the inhibition of mTOR (Ser-2481) and Akt (Ser-473) phosphorylation. Since mahanine treatment revealed this new insight of rictor-mTOR relationship, we examined an association between mTOR activation with rictor expression. Interestingly, in rictor knockdown (KD) NSCLC cells, mTOR activation was significantly impaired. Transfection of rictor over-expression vector into the NSCLC cells reversed this situation. In fact, both rictor KD and mahanine treated cells showed considerably depleted phospho-mTOR level. These results indicate that rictor is required to maintain constitutive activation of mTOR in lung cancer cells. When mTOR kinase activity in rictor KD cells was examined with Akt as substrate, a significant reduction of Akt phosphorylation indicated impairment of mTOR kinase potentiality. Disruption of mTOR and Akt activation caused drastic mortality of NSCLC cancer cells through apoptosis. Hence, our study reveals a new dimension in mTOR-rictor relationship, where rictor stands to be a suitable therapeutic target for lung cancer. Springer Science+Business Media New York, 2015 Lung cancer nationallicence Akt deactivation nationallicence mTORC2 nationallicence Rictor nationallicence Apoptosis nationallicence NSCLC : Non-small cell lung cancer nationallicence Rictor : Rapamycin insensitive companion of mTOR nationallicence mTOR : Mammalian target of rapamycin nationallicence mTORC2 : Mammalian target of rapamycin complex 2 nationallicence KD : Knock down nationallicence p-Akt : Phosphorylated Akt nationallicence PDK-1 : PI3K-dependent kinase-1 nationallicence DMEM : Dulbecco's-modified Eagle's medium nationallicence FBS : Fetal bovine serum nationallicence DMSO : Dimethyl sulfoxide nationallicence ASO : Antisense oligonucleotide nationallicence Q-PCR : Quantitative PCR nationallicence FITC : Fluorescein isothiocyanate nationallicence MTT : 3-(4,5-dimethylthiazol-2-yl)-2-5- diphenyltetrazolium bromide nationallicence PBS : Phosphate-buffered saline nationallicence Fhit : Fragile histidine triad nationallicence Chatterjee Priyajit Department of Zoology, School of Life Science, Visva-Bharati University, 731235, Santiniketan, India aut Seal Soma Department of Zoology, School of Life Science, Visva-Bharati University, 731235, Santiniketan, India aut Mukherjee Sandip Department of Zoology, School of Life Science, Visva-Bharati University, 731235, Santiniketan, India aut Kundu Rakesh Department of Zoology, School of Life Science, Visva-Bharati University, 731235, Santiniketan, India aut Bhuyan Mantu CSIR- North East Institute of Science & Technology, 785006, Jorhat, Assam, India aut Barua Nabin CSIR- North East Institute of Science & Technology, 785006, Jorhat, Assam, India aut Baruah Pranab CSIR- North East Institute of Science & Technology, 785006, Jorhat, Assam, India aut Babu Santi Department of Zoology, School of Life Science, Visva-Bharati University, 731235, Santiniketan, India aut Bhattacharya Samir Department of Zoology, School of Life Science, Visva-Bharati University, 731235, Santiniketan, India aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 149-158 0300-8177 405:1-2<149 2015 405 11010 https://doi.org/10.1007/s11010-015-2406-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2406-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chatterjee Priyajit Department of Zoology, School of Life Science, Visva-Bharati University, 731235, Santiniketan, India aut NATIONALLICENCE 700 1- Seal Soma Department of Zoology, School of Life Science, Visva-Bharati University, 731235, Santiniketan, India aut NATIONALLICENCE 700 1- Mukherjee Sandip Department of Zoology, School of Life Science, Visva-Bharati University, 731235, Santiniketan, India aut NATIONALLICENCE 700 1- Kundu Rakesh Department of Zoology, School of Life Science, Visva-Bharati University, 731235, Santiniketan, India aut NATIONALLICENCE 700 1- Bhuyan Mantu CSIR- North East Institute of Science & Technology, 785006, Jorhat, Assam, India aut NATIONALLICENCE 700 1- Barua Nabin CSIR- North East Institute of Science & Technology, 785006, Jorhat, Assam, India aut NATIONALLICENCE 700 1- Baruah Pranab CSIR- North East Institute of Science & Technology, 785006, Jorhat, Assam, India aut NATIONALLICENCE 700 1- Babu Santi Department of Zoology, School of Life Science, Visva-Bharati University, 731235, Santiniketan, India aut NATIONALLICENCE 700 1- Bhattacharya Samir Department of Zoology, School of Life Science, Visva-Bharati University, 731235, Santiniketan, India aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 149-158 0300-8177 405:1-2<149 2015 405 11010