Flavonoids induce apoptosis in human leukemia U937 cells through caspase- and caspase-calpain-dependent pathways

Alberto Monasterio, María C. Urdaci, Iryna Pinchuk, Natalia López-Moratalla, Juan J. Martínez-Irujo

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Flavonoids are polyphenolic phytochemicals that are ubiquitous in plants and present in the common human diet. They may exert diverse beneficial effects, including antioxidant and anticarcinogenic activities. In this study we tested the apoptotic activity of 22 flavonoids and related compounds in leukemic U937 cells. Several flavones but none of the isoflavones or flavanones tested induced apoptotic cell death under these conditions, as determined by reduction in cell viability, flow cytometry, and oligonucleosomal DNA fragmentation. Structure-activity relationship showed that at least two hydroxylations in positions 3, 5, and 7 of the A ring were needed to induce apoptosis, whereas hydroxylation in 3′ and/or 4′ of the B ring enhanced proapoptotic activity. At lower concentrations, these compounds were also able to sensitize these cells to apoptosis induced by tumor necrosis factor-α. Regarding the mechanisms, galangin, luteolin, chrysin, and quercetin induced apoptosis in a way that required the activation of caspases 3 and 8, but not caspase 9. In contrast, an active role of calpains in addition to caspases was demonstrated in apoptosis induced by fisetin, apigenin, and 3,7-dihydroxyflavone. Our data show evidence of the proapoptotic properties of some flavonoids that could support their rational use as chemopreventive and therapeutic agents against carcinogenic disease.

Original languageEnglish (US)
Pages (from-to)90-100
Number of pages11
JournalNutrition and Cancer
Volume50
Issue number1
StatePublished - 2004
Externally publishedYes

Fingerprint

U937 Cells
calpain
Calpain
caspases
Caspases
leukemia
Flavonoids
Leukemia
flavonoids
apoptosis
Apoptosis
hydroxylation
Hydroxylation
Flavanones
cells
Flavones
Apigenin
Luteolin
caspase-8
caspase-9

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Food Science

Cite this

Monasterio, A., Urdaci, M. C., Pinchuk, I., López-Moratalla, N., & Martínez-Irujo, J. J. (2004). Flavonoids induce apoptosis in human leukemia U937 cells through caspase- and caspase-calpain-dependent pathways. Nutrition and Cancer, 50(1), 90-100.

Flavonoids induce apoptosis in human leukemia U937 cells through caspase- and caspase-calpain-dependent pathways. / Monasterio, Alberto; Urdaci, María C.; Pinchuk, Iryna; López-Moratalla, Natalia; Martínez-Irujo, Juan J.

In: Nutrition and Cancer, Vol. 50, No. 1, 2004, p. 90-100.

Research output: Contribution to journalArticle

Monasterio, A, Urdaci, MC, Pinchuk, I, López-Moratalla, N & Martínez-Irujo, JJ 2004, 'Flavonoids induce apoptosis in human leukemia U937 cells through caspase- and caspase-calpain-dependent pathways', Nutrition and Cancer, vol. 50, no. 1, pp. 90-100.
Monasterio A, Urdaci MC, Pinchuk I, López-Moratalla N, Martínez-Irujo JJ. Flavonoids induce apoptosis in human leukemia U937 cells through caspase- and caspase-calpain-dependent pathways. Nutrition and Cancer. 2004;50(1):90-100.
Monasterio, Alberto ; Urdaci, María C. ; Pinchuk, Iryna ; López-Moratalla, Natalia ; Martínez-Irujo, Juan J. / Flavonoids induce apoptosis in human leukemia U937 cells through caspase- and caspase-calpain-dependent pathways. In: Nutrition and Cancer. 2004 ; Vol. 50, No. 1. pp. 90-100.
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