PMID- 25893736
OWN - NLM
STAT- MEDLINE
DCOM- 20160216
LR  - 20220409
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 405
IP  - 1-2
DP  - 2015 Jul
TI  - A carbazole alkaloid deactivates mTOR through the suppression of rictor and that 
      induces apoptosis in lung cancer cells.
PG  - 149-58
LID - 10.1007/s11010-015-2406-2 [doi]
AB  - 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.
FAU - Chatterjee, Priyajit
AU  - Chatterjee P
AD  - Department of Zoology, School of Life Science, Visva-Bharati University, 
      Santiniketan, 731235, India.
FAU - Seal, Soma
AU  - Seal S
FAU - Mukherjee, Sandip
AU  - Mukherjee S
FAU - Kundu, Rakesh
AU  - Kundu R
FAU - Bhuyan, Mantu
AU  - Bhuyan M
FAU - Barua, Nabin C
AU  - Barua NC
FAU - Baruah, Pranab K
AU  - Baruah PK
FAU - Babu, Santi Prasad Sinha
AU  - Babu SP
FAU - Bhattacharya, Samir
AU  - Bhattacharya S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150417
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Alkaloids)
RN  - 0 (Carbazoles)
RN  - 0 (Carrier Proteins)
RN  - 0 (RICTOR protein, human)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Alkaloids/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Carbazoles/*pharmacology
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism
MH  - Carrier Proteins/*metabolism
MH  - Cell Line, Tumor
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/metabolism
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rapamycin-Insensitive Companion of mTOR Protein
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2015/04/22 06:00
MHDA- 2016/02/18 06:00
CRDT- 2015/04/21 06:00
PHST- 2014/11/05 00:00 [received]
PHST- 2015/04/09 00:00 [accepted]
PHST- 2015/04/21 06:00 [entrez]
PHST- 2015/04/22 06:00 [pubmed]
PHST- 2016/02/18 06:00 [medline]
AID - 10.1007/s11010-015-2406-2 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2015 Jul;405(1-2):149-58. doi: 10.1007/s11010-015-2406-2. Epub 
      2015 Apr 17.