Abstract
Aims: The aim of this study was the characterization of the in vitro cytotoxic properties of a recently isolated diterpene compound, 7β-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.
| Original language | English |
|---|---|
| Article number | 116610 |
| Journal | Life Sciences |
| Volume | 232 |
| DOIs | |
| Publication status | Published - Sep 1 2019 |
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Keywords
- Breast
- Diterpenes
- ERBB2
- ERK1/2
- Mitochondria
- ROS
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)
Cite this
The novel diterpene 7β-acetoxy-20-hydroxy-19,20-epoxyroyleanone from Salvia corrugata shows complex cytotoxic activities against human breast epithelial cells. / Cortese, Katia; Marconi, Silvia; D'Alesio, Carolina; Calzia, Daniela; Panfoli, Isabella; Tavella, Sara; Aiello, Cinzia; Pedrelli, Francesca; Bisio, Angela; Castagnola, Patrizio.
In: Life Sciences, Vol. 232, 116610, 01.09.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The novel diterpene 7β-acetoxy-20-hydroxy-19,20-epoxyroyleanone from Salvia corrugata shows complex cytotoxic activities against human breast epithelial cells
AU - Cortese, Katia
AU - Marconi, Silvia
AU - D'Alesio, Carolina
AU - Calzia, Daniela
AU - Panfoli, Isabella
AU - Tavella, Sara
AU - Aiello, Cinzia
AU - Pedrelli, Francesca
AU - Bisio, Angela
AU - Castagnola, Patrizio
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Aims: The aim of this study was the characterization of the in vitro cytotoxic properties of a recently isolated diterpene compound, 7β-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.
AB - Aims: The aim of this study was the characterization of the in vitro cytotoxic properties of a recently isolated diterpene compound, 7β-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.
KW - Breast
KW - Diterpenes
KW - ERBB2
KW - ERK1/2
KW - Mitochondria
KW - ROS
UR - http://www.scopus.com/inward/record.url?scp=85068070627&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068070627&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2019.116610
DO - 10.1016/j.lfs.2019.116610
M3 - Article
AN - SCOPUS:85068070627
VL - 232
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
M1 - 116610
ER -