A Subpopulation of the K562 Cells Are Killed by Curcumin Treatment after G2/M Arrest and Mitotic Catastrophe.
Curcumin is extensively investigated as a good chemo-preventive agent in the development of many cancers and particularly in leukemia, including treatment of chronic myelogenous leukemia and it has been proposed as an adjuvant for leukemia therapies. Human chronic myeloid leukemia cells (K562), were treated with 20 μM of curcumin, and we found that a subpopulation of these cells were arrested and accumulate in the G2/M phase of the cell cycle. Characterization of this cell subpopulation showed that the arrested cells presented nuclear morphology changes resembling those described for mitotic catastrophe. Mitotic cells displayed abnormal chromatin organization, collapse of the mitotic spindle and abnormal chromosome segregation. Then, these cells died in an apoptosis dependent manner and showed diminution in the protein levels of BCL-2 and XIAP. Moreover, our results shown that a transient activation of the nuclear factor κB (NFκB) occurred early in these cells, but decreased after 6 h of the treatment, explaining in part the diminution of the anti-apoptotic proteins. Additionally, P73 was translocated to the cell nuclei, because the expression of the C/EBPα, a cognate repressor of the P73 gene, was decreased, suggesting that apoptosis is trigger by elevation of P73 protein levels acting in concert with the diminution of the two anti-apoptotic molecules. In summary, curcumin treatment might produce a P73-dependent apoptotic cell death in chronic myelogenous leukemia cells (K562), which was triggered by mitotic catastrophe, due to sustained BAX and survivin expression and impairment of the anti-apoptotic proteins BCL-2 and XIAP.
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, Mexico City, Mexico.
Macario
M
Martinez-Castillo
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, Mexico City, Mexico.
Raul
R
Bonilla-Moreno
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, Mexico City, Mexico.
Leticia
L
Aleman-Lazarini
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, Mexico City, Mexico.
Marco Antonio
MA
Meraz-Rios
Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Secretaria de Salud, Mexico City, México.
Lorena
L
Orozco
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, Mexico City, Mexico.
Leticia
L
Cedillo-Barron
Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Secretaria de Salud, Mexico City, México.
Emilio J
EJ
Cordova
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados, Mexico City, Mexico.
Nicolas
http://orcid.org/0000-0001-9489-2545
N
Villegas-Sepulveda
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects
D000970:Antineoplastic Agents; D003474:Curcumin