Curcumin binds tubulin, induces mitotic catastrophe, and impedes normal endothelial cell proliferation.
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.
U.S. Army Research Institute of Environmental Medicine, Military Nutrition Division, 15 Kansas Street, Natick, MA 01760, United States. Electronic address: steven.jackson25@us.army.mil.
Steven J T
SJ
Jackson
Laura L
LL
Murphy
Richard C
RC
Venema
Keith W
KW
Singletary
Andrew J
AJ
Young
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002417:Cattle; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects*; D014404:Tubulin / Q000378:metabolism*
D000975:Antioxidants; D014404:Tubulin; D051547:Heme Oxygenase-1; D003474:Curcumin
BAE; CMN; Cell cycle; Curcumin; Endothelial; HO-1; Tubulin; bovine aortic endothelial; curcumin; hemeoxygenase-1