PMID- 29960020
OWN - NLM
STAT- MEDLINE
DCOM- 20181120
LR  - 20181120
IS  - 1873-6351 (Electronic)
IS  - 0278-6915 (Linking)
VI  - 120
DP  - 2018 Oct
TI  - Anti-proliferative activity-guided isolation of clerodermic acid from Salvia 
      nemorosa L.: Geno/cytotoxicity and hypoxia-mediated mechanism of action.
PG  - 155-163
LID - S0278-6915(18)30434-4 [pii]
LID - 10.1016/j.fct.2018.06.060 [doi]
AB  - The adaptation of solid tumors to the low oxygen/nutrient environment is mediated 
      by the pivotal transcription role of hypoxia-inducible factor-1 (HIF-1). Thus, 
      the HIF-1 and its subunits have been considered to be hopeful anti-cancer 
      targets. Various natural compounds were reported to persuade cell cytotoxicity 
      through targeting and downregulation of the HIF-1. The genus Salvia is a rich 
      source of bioactive terpenoids which show promising anti-cancer activities. Here, 
      the identification of natural anti-proliferative compound targeting the HIF-1alpha 
      expression was reported. A bioassay-guided isolation was employed for the 
      discovery of natural anti-proliferative compounds from Salvia extracts using MTT 
      assay against A549 cells. In this direction, clerodermic acid (CDA) as a potent 
      cytotoxic compound was purified from Salvia nemorosa and identified using 1D and 
      2D NMR analysis. Results indicated that CDA has anti-proliferation activity 
      (IC(50) value of 35 mug/mL) which was confirmed by genotoxicity and apoptosis 
      detection analyses. The quantitative qPCR analysis showed that the expression 
      level of HIF-1 alpha was strongly inhibited in the hypoxic cells treated with CDA 
      compared to the untreated cells tolerated hypoxia. Findings exhibited that S. 
      nemorosa and clerodermic acid have significant potential for reducing HIF-1alpha 
      expression and could be considered for further studies for cancer therapy.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Bahadori, Mir Babak
AU  - Bahadori MB
AD  - Phytopharmacology Research Center, Maragheh University of Medical Sciences, 
      Maragheh, Iran.
FAU - Eskandani, Morteza
AU  - Eskandani M
AD  - Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz 
      University of Medical Sciences, Tabriz, Iran. Electronic address: 
      morteza.eskandani@gmail.com.
FAU - De Mieri, Maria
AU  - De Mieri M
AD  - Division of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, 
      4056, Basel, Switzerland.
FAU - Hamburger, Matthias
AU  - Hamburger M
AD  - Division of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, 
      4056, Basel, Switzerland.
FAU - Nazemiyeh, Hossein
AU  - Nazemiyeh H
AD  - Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz 
      University of Medical Sciences, Tabriz, Iran; Departement of Pharmacognosy, 
      Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. 
      Electronic address: nazemiyehh@yahoo.com.
LA  - eng
PT  - Journal Article
DEP - 20180628
PL  - England
TA  - Food Chem Toxicol
JT  - Food and chemical toxicology : an international journal published for the British 
      Industrial Biological Research Association
JID - 8207483
RN  - 0 (Annexin A5)
RN  - 0 (Carcinogens)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Lactones)
RN  - 0 (Mutagens)
RN  - 0 (Naphthalenes)
RN  - 0 (RNA, Messenger)
RN  - 0 (clerodermic acid)
SB  - IM
MH  - A549 Cells
MH  - Annexin A5/metabolism
MH  - Apoptosis/drug effects
MH  - Biological Assay
MH  - Carcinogens/*pharmacology
MH  - Cell Proliferation/*drug effects
MH  - Down-Regulation
MH  - Humans
MH  - Hypoxia/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - Inhibitory Concentration 50
MH  - Lactones/chemistry/*pharmacology
MH  - Magnetic Resonance Spectroscopy
MH  - Molecular Structure
MH  - Mutagens/*pharmacology
MH  - Naphthalenes/chemistry/*pharmacology
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Salvia/*chemistry
OTO - NOTNLM
OT  - Anti-cancer
OT  - Bioassay-guided isolation
OT  - Clerodane diterpenoid
OT  - HIF-1alpha
OT  - Hypoxia
OT  - Salvia
EDAT- 2018/07/01 06:00
MHDA- 2018/11/21 06:00
CRDT- 2018/07/01 06:00
PHST- 2018/05/05 00:00 [received]
PHST- 2018/06/22 00:00 [revised]
PHST- 2018/06/26 00:00 [accepted]
PHST- 2018/07/01 06:00 [pubmed]
PHST- 2018/11/21 06:00 [medline]
PHST- 2018/07/01 06:00 [entrez]
AID - S0278-6915(18)30434-4 [pii]
AID - 10.1016/j.fct.2018.06.060 [doi]
PST - ppublish
SO  - Food Chem Toxicol. 2018 Oct;120:155-163. doi: 10.1016/j.fct.2018.06.060. Epub 
      2018 Jun 28.