PMID- 31254584
OWN - NLM
STAT- MEDLINE
DCOM- 20190924
LR  - 20211204
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 232
DP  - 2019 Sep 1
TI  - The novel diterpene 7beta-acetoxy-20-hydroxy-19,20-epoxyroyleanone from Salvia 
      corrugata shows complex cytotoxic activities against human breast epithelial 
      cells.
PG  - 116610
LID - S0024-3205(19)30536-3 [pii]
LID - 10.1016/j.lfs.2019.116610 [doi]
AB  - AIMS: The aim of this study was the characterization of the in vitro cytotoxic 
      properties of a recently isolated diterpene compound, 
      7beta-acetoxy-20-hydroxy-19,20-epoxyroyleanone (compound 1), extracted from Salvia 
      corrugata, versus human cell lines. MAIN METHODS: We used as model study 
      immortalized breast epithelial cells MCF10A and two ERBB2(+) breast cancer (BCa) 
      cell lines, SKBR-3 and BT474. Compound 1 was isolated by methanolic extraction 
      from regenerated shoots of Salvia corrugata Vahl, and purified by high pressure 
      liquid chromatography (HPLC). Flow cytometry (FCM) was employed for cell cycle, 
      apoptosis and reactive oxygen species (ROS) analysis. Cell morphology was 
      assessed by immunofluorescence and transmission electron microscopy (TEM). KEY 
      FINDINGS: Compound 1 inhibited cell survival of all breast cell lines. In 
      particular, compound 1 promoted cell cycle arrest in the G0/G1 phase and 
      apoptosis along with impairment of the mitochondrial function, which was 
      reflected in a gross alteration of the mitochondrial network structure. 
      Furthermore, we also detected a potent activation of the ERK1/2 kinase, which 
      suggested the induction of reactive oxygen species (ROS). Partial rescue of 
      survival obtained with n-acetylcysteine (NAC) when coadminstered with compound 1 
      further supported a contribution of ROS mediated mechanisms to the growth-arrest 
      and proapoptotic activity of compound 1 in both BCa cell lines. ROS production 
      was indeed confirmed in SKBR-3. SIGNIFICANCE: Our findings show that compound 1 
      has a cytotoxic activity against both human normal and cancer cell lines derived 
      from breast epithelia, which is mediated by ROS generation and mitochondrial 
      damage.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Cortese, Katia
AU  - Cortese K
AD  - DIMES, Department of Experimental Medicine, Human Anatomy, University of Genoa, 
      Genoa, Italy. Electronic address: cortesek@unige.it.
FAU - Marconi, Silvia
AU  - Marconi S
AD  - DIMES, Department of Experimental Medicine, Human Anatomy, University of Genoa, 
      Genoa, Italy.
FAU - D'Alesio, Carolina
AU  - D'Alesio C
AD  - DiMI, Department of Internal Medicine and Medical Specialties, University of 
      Genoa, Genoa, Italy.
FAU - Calzia, Daniela
AU  - Calzia D
AD  - DIFAR, Department of Pharmacy, University of Genoa, Genoa, Italy.
FAU - Panfoli, Isabella
AU  - Panfoli I
AD  - DIFAR, Department of Pharmacy, University of Genoa, Genoa, Italy.
FAU - Tavella, Sara
AU  - Tavella S
AD  - DIMES, Department of Experimental Medicine, Human Anatomy, University of Genoa, 
      Genoa, Italy; Department of Integrated Oncological Therapies, IRCCS Ospedale 
      Policlinico San Martino, Genoa, Italy.
FAU - Aiello, Cinzia
AU  - Aiello C
AD  - Department of Integrated Oncological Therapies, IRCCS Ospedale Policlinico San 
      Martino, Genoa, Italy.
FAU - Pedrelli, Francesca
AU  - Pedrelli F
AD  - DIFAR, Department of Pharmacy, University of Genoa, Genoa, Italy.
FAU - Bisio, Angela
AU  - Bisio A
AD  - DIFAR, Department of Pharmacy, University of Genoa, Genoa, Italy.
FAU - Castagnola, Patrizio
AU  - Castagnola P
AD  - Department of Integrated Oncological Therapies, IRCCS Ospedale Policlinico San 
      Martino, Genoa, Italy.
LA  - eng
PT  - Journal Article
DEP - 20190627
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Camphanes)
RN  - 0 (Diterpenes)
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (danshen dripping pill)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Breast/cytology/*drug effects/metabolism
MH  - Camphanes
MH  - Cell Cycle/drug effects
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Division/drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Diterpenes/isolation & purification/*pharmacology
MH  - Drugs, Chinese Herbal/*pharmacology
MH  - Epithelial Cells/*drug effects/metabolism
MH  - Female
MH  - Humans
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mitochondria/drug effects/metabolism
MH  - Panax notoginseng
MH  - Reactive Oxygen Species/metabolism
MH  - Resting Phase, Cell Cycle/drug effects
MH  - Salvia miltiorrhiza
OTO - NOTNLM
OT  - Breast
OT  - Diterpenes
OT  - ERBB2
OT  - ERK1/2
OT  - Mitochondria
OT  - ROS
EDAT- 2019/06/30 06:00
MHDA- 2019/09/26 06:00
CRDT- 2019/06/30 06:00
PHST- 2019/03/27 00:00 [received]
PHST- 2019/06/25 00:00 [revised]
PHST- 2019/06/26 00:00 [accepted]
PHST- 2019/06/30 06:00 [pubmed]
PHST- 2019/09/26 06:00 [medline]
PHST- 2019/06/30 06:00 [entrez]
AID - S0024-3205(19)30536-3 [pii]
AID - 10.1016/j.lfs.2019.116610 [doi]
PST - ppublish
SO  - Life Sci. 2019 Sep 1;232:116610. doi: 10.1016/j.lfs.2019.116610. Epub 2019 Jun 
      27.