TY - JOUR
T1 - Anti-angiogenic properties of cafestol and kahweol palmitate diterpene esters
AU - Moeenfard, Marzieh
AU - Cortez, Alice
AU - Machado, Vera
AU - Costa, Raquel
AU - Luís, Carla
AU - Coelho, Pedro
AU - Soares, Raquel
AU - Alves, Arminda
AU - Borges, Nuno
AU - Santos, Alejandro
N1 - Funding Information:
This study was partially funded by FCT (UID/BIM/04293/2013). This work was also financially supported by Project UID/EQU/00511/2013-LEPABE (Laboratory for Process Engineering, Environment, Biotechnology and Energy—EQU/00511) by FEDER funds through “Programa Operacional Competitividade e Internacionalização”—COMPETE2020 and by national funds through FCT—“Fundação para a Ciência e a Tecnologia,” SFRH/BD/79318/2011. Furthermore, the authors thank our collaborators namely Janete dos Santos, Maria Inês Martins, Astrid Vernemmer, Cláudia Mendes, Carolina Silva, and Ana Rita Rocha for their support in the present research study and their valuable comments during the work.
Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Epidemiological studies support the association of coffee-specific diterpenes, with various beneficial health effects. Although anti-antiangiogenic properties of free cafestol and kahweol have been recently described, available data regarding their esterified form, in particular palmitate esters as the main diterpene esters present in coffee, are still rare. Given that angiogenesis plays an important role in many pathological conditions, including cancer growth and metastasis, this study aimed to assess and compare the potential anti-angiogenic effects of cafestol palmitate (CP) and kahweol palmitate (KP) in an in vitro angiogenesis model. According to our findings, both compounds inhibited angiogenesis steps on human microvascular endothelial cells (HMVECs), although a more significant effect was observed for KP. Compared to control, HMVECs viability decreased in a dose-dependent manner upon incubation either with CP or KP. Concentrations of 75 and 100 μM of each compound were cytotoxic. Cell proliferation was also dramatically reduced by both diterpene esters at 50 μM, although KP had a stronger inhibitory effect. However, CP and KP did not induce apoptosis on HMVECs. Both compounds reduced cell migration, but this effect was only statistically significant after KP incubation. Inhibition of VEGFR2 expression and its downstream effector Akt, but not Erk, was also observed in CP- and KP-treated HMVECs. These findings were confirmed using ELISA assay for phosphorylated (active) VEGFR-2. Taken together, these data indicate that both CP and KP can be considered potent compounds against angiogenesis-dependent disorders. Our findings further indicate that KP exerts more potent anti-angiogenic effects than CP, in most of assays. J. Cell. Biochem. 117: 2748–2756, 2016.
AB - Epidemiological studies support the association of coffee-specific diterpenes, with various beneficial health effects. Although anti-antiangiogenic properties of free cafestol and kahweol have been recently described, available data regarding their esterified form, in particular palmitate esters as the main diterpene esters present in coffee, are still rare. Given that angiogenesis plays an important role in many pathological conditions, including cancer growth and metastasis, this study aimed to assess and compare the potential anti-angiogenic effects of cafestol palmitate (CP) and kahweol palmitate (KP) in an in vitro angiogenesis model. According to our findings, both compounds inhibited angiogenesis steps on human microvascular endothelial cells (HMVECs), although a more significant effect was observed for KP. Compared to control, HMVECs viability decreased in a dose-dependent manner upon incubation either with CP or KP. Concentrations of 75 and 100 μM of each compound were cytotoxic. Cell proliferation was also dramatically reduced by both diterpene esters at 50 μM, although KP had a stronger inhibitory effect. However, CP and KP did not induce apoptosis on HMVECs. Both compounds reduced cell migration, but this effect was only statistically significant after KP incubation. Inhibition of VEGFR2 expression and its downstream effector Akt, but not Erk, was also observed in CP- and KP-treated HMVECs. These findings were confirmed using ELISA assay for phosphorylated (active) VEGFR-2. Taken together, these data indicate that both CP and KP can be considered potent compounds against angiogenesis-dependent disorders. Our findings further indicate that KP exerts more potent anti-angiogenic effects than CP, in most of assays. J. Cell. Biochem. 117: 2748–2756, 2016.
KW - Angiogenesis
KW - Coffee fat-soluble compounds
KW - Esterified diterpenes
KW - HMVEC
UR - http://www.scopus.com/inward/record.url?scp=85027947489&partnerID=8YFLogxK
U2 - 10.1002/jcb.25573
DO - 10.1002/jcb.25573
M3 - Article
C2 - 27129115
AN - SCOPUS:85027947489
SN - 0730-2312
SP - 2748
EP - 2756
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
ER -