PMID- 24267912
OWN - NLM
STAT- MEDLINE
DCOM- 20140318
LR  - 20211021
IS  - 1365-2184 (Electronic)
IS  - 0960-7722 (Print)
IS  - 0960-7722 (Linking)
VI  - 47
IP  - 1
DP  - 2014 Feb
TI  - Flavonol isolated from ethanolic leaf extract of Thuja occidentalis arrests the 
      cell cycle at G2-M and induces ROS-independent apoptosis in A549 cells, targeting 
      nuclear DNA.
PG  - 56-71
LID - 10.1111/cpr.12079 [doi]
AB  - OBJECTIVES: The K-ras gene mutation commonly found in lung adenocarcinomas 
      contributes to their non-invasive expansion. Our main objective here was to 
      develop a chemopreventive agent against K-ras-mutated lung adenocarcinoma cell 
      line like-A549. MATERIALS AND METHODS: We isolated flavonol from ethanolic leaf 
      extract of Thuja occidentalis, and evaluated its apoptotic potentials on A549 
      cells. They were treated with 1-10 mug/ml of flavonol and viability was tested 
      retaining normal lung cells L-132 as control. We performed assays such as TUNEL, 
      annexin V, cell-cycle and mitochondrial membrane potentials, by FACS analysis. 
      ROS-mediated oxidative stress and drug-DNA interactions were analysed along with 
      gene expression studies for p53, Bax-Bcl2, cytochrome c, the caspase cascade 
      genes and PARP. RESULTS: Flavonol reduced A549 cell viability in a dose- and 
      time-dependent manner (IC50 value = 7.6 +/- 0.05 mug/ml following 48 h incubation) 
      sparing normal L-132 cells. It effected G2-M phase cell cycle arrest and 
      apoptosis, as indicated by progressive increase in the sub-G1, annexin V and 
      TUNEL-positive cell populations. Apoptotic effects appeared to be 
      mitochondria-dependent, caspase-3-mediated, but ROS-independent. Analysis of 
      circular dichroism data revealed that flavonol intercalated with nuclear DNA. In 
      vivo studies on non small cell lung carcinoma (NSCLC)-induced mice confirmed 
      anti-cancer potential of flavonol. CONCLUSION: Flavonol-induced apoptosis 
      apparently resulted from intercalation of cells' nuclear DNA. Flavonol inhibited 
      growth of induced lung tumours in the mice, indicating its potential as an 
      effective agent against NSCLC.
CI  - (c) 2013 John Wiley & Sons Ltd.
FAU - Mukherjee, A
AU  - Mukherjee A
AD  - Department of Zoology, Cytogenetics and Molecular Biology Laboratory, University 
      of Kalyani, Kalyani, West Bengal, 741235, India.
FAU - Sikdar, S
AU  - Sikdar S
FAU - Bishayee, K
AU  - Bishayee K
FAU - Boujedaini, N
AU  - Boujedaini N
FAU - Khuda-Bukhsh, A R
AU  - Khuda-Bukhsh AR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131123
PL  - England
TA  - Cell Prolif
JT  - Cell proliferation
JID - 9105195
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Flavonols)
RN  - 0 (Plant Extracts)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Adenocarcinoma/*drug therapy/pathology
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/isolation & purification/pharmacology
MH  - Apoptosis/*drug effects/genetics
MH  - Carcinoma, Non-Small-Cell Lung/drug therapy/pathology
MH  - Cell Cycle Checkpoints/*drug effects
MH  - Cell Division/drug effects
MH  - Cell Survival/drug effects
MH  - DNA, Neoplasm/drug effects
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Flavonols/isolation & purification/*pharmacology
MH  - G2 Phase/drug effects
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Mice
MH  - Plant Extracts/isolation & purification/pharmacology
MH  - Plant Leaves/chemistry
MH  - Reactive Oxygen Species/metabolism
MH  - Thuja/*chemistry
PMC - PMC6496600
COIS- None declared.
EDAT- 2013/11/26 06:00
MHDA- 2014/03/19 06:00
PMCR- 2013/11/23
CRDT- 2013/11/26 06:00
PHST- 2013/07/11 00:00 [received]
PHST- 2013/09/06 00:00 [accepted]
PHST- 2013/11/26 06:00 [entrez]
PHST- 2013/11/26 06:00 [pubmed]
PHST- 2014/03/19 06:00 [medline]
PHST- 2013/11/23 00:00 [pmc-release]
AID - CPR12079 [pii]
AID - 10.1111/cpr.12079 [doi]
PST - ppublish
SO  - Cell Prolif. 2014 Feb;47(1):56-71. doi: 10.1111/cpr.12079. Epub 2013 Nov 23.