Curcumin inhibits cell motility and alters microfilament organization and function in prostate cancer cells.
Curcumin is a dietary phytochemical associated with anti-tumorigenic effects, but the mechanisms by which it inhibits cancer cell growth and metastasis are not completely understood. For example, little information is available regarding the effects of curcumin on cytoskeletal organization and function. In this study, time-lapse video and immunofluorescence labeling methods were used to demonstrate that curcumin significantly alters microfilament organization and cell motility in PC-3 and LNCaP human prostate cancer cells in vitro. Curcumin rapidly arrests cell movements and subsequently alters cell shape in the highly motile PC-3 cell line, but has a less noticeable effect on the relatively immobile LNCaP cell line. Stress fibers are augmented, and the overall quantity of f-actin appears to increase in both types of cells following curcumin treatment. Cytochalasin B (CB) disrupts microfilament organization in both cell lines, and causes vigorous membrane blebbing in PC-3 cells, but not LNCaP cells. Pre-treatment of cells with curcumin suppresses changes in microfilament organization caused by CB, and blocks PC-3 membrane blebbing. At least some of the effects of curcumin appear to be mediated by protein kinase C (PKC), as treatment with the PKC inhibitor bisindolylmaleimide inhibits the ability of curcumin to block CB-induced membrane blebbing. These findings demonstrate that curcumin exerts significant effects on the actin cytoskeleton in prostate cancer cells, including altering microfilament organization and function. This is a novel observation that may represent an important mechanism by which curcumin functions as a chemopreventative agent, and as an inhibitor of angiogenesis and metastasis.
Holy
Jon
J
Department of Anatomy and Cell Biology, University of Minnesota School of Medicine, Duluth, MN, USA. jholy@d.umn.edu
D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000648:ultrastructure; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008857:Microscopy, Interference; D011471:Prostatic Neoplasms / Q000473:pathology / Q000648:ultrastructure*; D013997:Time Factors
D000970:Antineoplastic Agents; D003474:Curcumin