TY - JOUR
T1 - Curcumin binds tubulin, induces mitotic catastrophe, and impedes normal endothelial cell proliferation
AU - Jackson, Steven J.T.
AU - Murphy, Laura L.
AU - Venema, Richard C.
AU - Singletary, Keith W.
AU - Young, Andrew J.
PY - 2013/10
Y1 - 2013/10
N2 - Curcumin, a component of turmeric spice that imparts flavor and color to curry, is thought to possess anti-inflammatory and antioxidant properties in biological tissues. However, while such efficacies have been described in the context of carcinogenesis, the impact of curcumin on normal cell cycle regulation is poorly understood. Here, we provide evidence of curcumin toxicity in proliferating bovine aortic endothelial cells, at concentrations relevant to the diet and below those previously reported in cancer models. Upon confirming curcumin's ability to upregulate hemeoxygenase-1 in a dose-dependent fashion, we found the minimally efficacious curcumin concentration to also inhibit endothelial cell DNA synthesis. Moreover, curcumin concentrations below the minimum 2. μM threshold required to induce hemeoxygenase-1 bound tubulin protein in vitro and triggered hallmark evidence of mitotic catastrophe in vivo. Concentrations as low as 0.1. μM curcumin led to disproportionate DNA segregation, karyorrhexis, and micronucleation in proliferating endothelial cells. While suggesting a mechanism by which physiological curcumin concentrations inhibit cell cycle progression, these findings describe heretofore unappreciated curcumin toxicity with potential implications for endothelial growth, development, and tissue healing.
AB - Curcumin, a component of turmeric spice that imparts flavor and color to curry, is thought to possess anti-inflammatory and antioxidant properties in biological tissues. However, while such efficacies have been described in the context of carcinogenesis, the impact of curcumin on normal cell cycle regulation is poorly understood. Here, we provide evidence of curcumin toxicity in proliferating bovine aortic endothelial cells, at concentrations relevant to the diet and below those previously reported in cancer models. Upon confirming curcumin's ability to upregulate hemeoxygenase-1 in a dose-dependent fashion, we found the minimally efficacious curcumin concentration to also inhibit endothelial cell DNA synthesis. Moreover, curcumin concentrations below the minimum 2. μM threshold required to induce hemeoxygenase-1 bound tubulin protein in vitro and triggered hallmark evidence of mitotic catastrophe in vivo. Concentrations as low as 0.1. μM curcumin led to disproportionate DNA segregation, karyorrhexis, and micronucleation in proliferating endothelial cells. While suggesting a mechanism by which physiological curcumin concentrations inhibit cell cycle progression, these findings describe heretofore unappreciated curcumin toxicity with potential implications for endothelial growth, development, and tissue healing.
KW - Cell cycle
KW - Curcumin
KW - Endothelial
KW - Tubulin
UR - http://www.scopus.com/inward/record.url?scp=84883232795&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883232795&partnerID=8YFLogxK
U2 - 10.1016/j.fct.2013.08.008
DO - 10.1016/j.fct.2013.08.008
M3 - Article
C2 - 23939039
AN - SCOPUS:84883232795
SN - 0278-6915
VL - 60
SP - 431
EP - 438
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
ER -