Curcumin induces cell cycle arrest and apoptosis in human osteosarcoma (HOS) cells.
BACKGROUND
Curcumin is a major component of Curcuma longa rhizome and has been used as a traditional medicine for centuries. In this study, we showed that curcumin induced cell cycle arrest followed by antiproliferation and apoptosis in human osteosarcoma (HOS) cells.


METHODS
Antiproliferative activity was measured with the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Nuclear fragmentation was observed with a fluorescence microscope. Flow cytometry was performed to observe cell cycle distribution and apoptotic body appearance. Changes in cell cycle regulatory and apoptosis-related proteins were investigated by Western blot analysis.


RESULTS
The IC(50) value of curcumin was approximately 4.0 microg/ml. Induction of apoptosis was evidenced by apoptotic body appearance and chromosomal DNA degradation. Flow-cytometric analysis indicated that curcumin induced successive G(1)/S and G(2)/M phase arrest followed by apoptosis in HOS cells. The G(1)/S and G(2)/S phase arrest was accompanied by down-regulation of cyclin D1, cdc2 and cyclin B1, respectively. Apoptosis was induced by capspase-3 activation and poly(ADP-ribosyl)polymerase (PARP) cleavage.


CONCLUSIONS
Our results demonstrated that curcumin caused death of HOS cells by blocking cells successively in G(1)/S and G(2)/M phases and activating the caspase-3 pathway.
Lee
Duk Su
DS
Department of Biochemistry, School of Dentistry, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-Ku, Seoul 130-701, Korea.
Lee
Mi Kyoung
MK
Kim
Jeong Hee
JH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D003474:Curcumin