PMID- 30361692
OWN - NLM
STAT- MEDLINE
DCOM- 20191018
LR  - 20191210
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Oct 25
TI  - In-vitro evaluation of apoptotic effect of OEO and thymol in 2D and 3D cell 
      cultures and the study of their interaction mode with DNA.
PG  - 15787
LID - 10.1038/s41598-018-34055-w [doi]
LID - 15787
AB  - Oliveria decumbens is an Iranian endemic plant used extensively in traditional 
      medicine. Recently, some studies have been performed on biological effects of 
      Oliveria essential oil (OEO). However, to our knowledge, the anticancer activity 
      of OEO has not been reported. Based on our GC/MS analysis, the basic ingredients 
      of OEO are thymol, carvacrol, p-cymene and gamma-terpinene. Therefore, we used OEO 
      and its main component, thymol, to explore their effects on cell growth 
      inhibition and anticancer activity. Despite having a limited effect on L929 
      normal cells, OEO/thymol induced cytotoxicity in MDA-MB231 breast cancer 
      monolayers (2D) and to a lesser extent in MDA-MB231 spheroids (3D). Flow 
      cytometry, caspase-3 activity assay in treated monolayers/spheroids and also 
      fluorescence staining and DNA fragmentation in treated monolayers demonstrated 
      apoptotic death mode. Indeed, OEO/thymol increased the Reactive Oxygen Species 
      (ROS) level leading to mitochondrial membrane potential (MMP, DeltaPsim) loss, 
      caspase-3 activation and DNA damage caused S-phase cell cycle arrest. 
      Furthermore, immunoblotting studies revealed the activation of intrinsic and 
      maybe extrinsic apoptosis pathways by OEO/thymol. Additionally, in-vitro 
      experiments, indicated that OEO/thymol interacts with DNA via minor grooves 
      confirmed by docking method. Altogether, our reports underlined the potential of 
      OEO to be considered as a new candidate for cancer therapy.
FAU - Jamali, Tahereh
AU  - Jamali T
AD  - Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
FAU - Kavoosi, Gholamreza
AU  - Kavoosi G
AD  - Institute of Biotechnology, Shiraz University, Shiraz, Iran.
FAU - Safavi, Maliheh
AU  - Safavi M
AD  - Department of Biotechnology, Iranian Research Organization for Science and 
      Technology, Tehran, Iran.
FAU - Ardestani, Susan K
AU  - Ardestani SK
AD  - Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. 
      ardestany@ut.ac.ir.
LA  - eng
PT  - Journal Article
DEP - 20181025
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Oils, Volatile)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 3J50XA376E (Thymol)
RN  - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine)
RN  - 9007-49-2 (DNA)
RN  - EC 3.4.22.- (Caspase 3)
RN  - G9481N71RO (Deoxyguanosine)
SB  - IM
MH  - 8-Hydroxy-2'-Deoxyguanosine
MH  - Animals
MH  - Apiaceae/*chemistry
MH  - Apoptosis/*drug effects
MH  - Caspase 3/metabolism
MH  - Cell Culture Techniques/*methods
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - DNA/chemistry/*metabolism
MH  - DNA Fragmentation/drug effects
MH  - Deoxyguanosine/analogs & derivatives/metabolism
MH  - Gas Chromatography-Mass Spectrometry
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Intracellular Space/metabolism
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mice
MH  - Molecular Docking Simulation
MH  - Nucleic Acid Conformation
MH  - Oils, Volatile/chemistry/*pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Spheroids, Cellular/drug effects
MH  - Thymol/*pharmacology
MH  - bcl-2-Associated X Protein/metabolism
PMC - PMC6202332
COIS- The authors declare no competing interests.
EDAT- 2018/10/27 06:00
MHDA- 2019/10/19 06:00
PMCR- 2018/10/25
CRDT- 2018/10/27 06:00
PHST- 2018/05/11 00:00 [received]
PHST- 2018/09/10 00:00 [accepted]
PHST- 2018/10/27 06:00 [entrez]
PHST- 2018/10/27 06:00 [pubmed]
PHST- 2019/10/19 06:00 [medline]
PHST- 2018/10/25 00:00 [pmc-release]
AID - 10.1038/s41598-018-34055-w [pii]
AID - 34055 [pii]
AID - 10.1038/s41598-018-34055-w [doi]
PST - epublish
SO  - Sci Rep. 2018 Oct 25;8(1):15787. doi: 10.1038/s41598-018-34055-w.