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Updated: Jun 16, 2026

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages
Published on: April 6, 2022
5,7,3'-trihydroxy-3,4'-dimethoxyflavone-induced cell death in human leukemia cells is dependent on caspases and
Fernando Torres1, José Quintana, Francisco Estévez
1Department of Biochemistry and Molecular Biology, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
Abstract:
Flavonoids are polyphenolic compounds which display a vast array of biological activities and are promising anticancer agents. In this study we investigated the effect of 5,7,3'-trihydroxy-3,4'-dimethoxyflavone (THDF) on viability of nine human tumor cell lines and found that it was highly cytotoxic against leukemia cells. THDF induced G(2)-M phase cell-cycle arrest and apoptosis through a caspase-dependent mechanism involving cytochrome c release, processing of multiple caspases (caspase-3, -6, -7, and -9) and cleavage of poly(ADP-ribose) polymerase. Overexpression of the protective mitochondrial proteins Bcl-2 and Bcl-x(L) conferred partial resistance to THDF-induced apoptosis. This flavonoid induced the phosphorylation of members of the mitogen-activated protein kinases (MAPKs) family and cell death was attenuated by inhibition of c-jun N-terminal kinases/stress-activated protein kinases (JNK/SAPK) and of extracellular signal-regulated kinases (ERK) 1/2. In the present study we report that THDF-induced cell death is mediated by an intrinsic dependent apoptotic event involving mitochondria and MAPKs, and through a mechanism independent of the generation of reactive oxygen species. The results suggest that THDF could be useful in the development of novel anticancer agents.
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