Piceatannol, a hydroxylated analog of the chemopreventive agent resveratrol, is a potent inducer of apoptosis in the lymphoma cell line BJAB and in primary, leukemic lymphoblasts

Abstract

The stilbene phytochemicals resveratrol and piceatannol have been reported to possess substantial antitumorigenic and antileukemic activities, respectively. Although recent experimental data revealed the proapoptotic potency of resveratrol, the molecular mechanisms underlying the antileukemic activity have not yet been studied in detail. In the present study, we show that resveratrol, as well as the hydroxylated analog piceatannol, are potent inducers of apoptotic cell death in BJAB Burkittlike lymphoma cells with an ED 50 concentration of 25 M. Further experiments revealed that treatment of BJAB cells with both substances led to a concentration-dependent activation of caspase-3 and mitochondrial permeability transition. Using BJAB cells overexpressing a dominant-negative mutant of the Fas-associated death domain (FADD) adaptor protein to block death receptor-mediated apoptosis, we demonstrate that resveratrol-and piceatannol-induced cell death in these cells is independent of the CD95/Fas signaling pathway. To explore the antileukemic properties of both compounds in more detail, we extended our study to primary, leukemic lymphoblasts. Interestingly, piceatannol but not resveratrol is a very efficient inducer of apoptosis in this ex vivo assay with leukemic lymphoblasts of 21 patients suffering from childhood lymphoblastic leukemia (ALL). Leukemia (2001Leukemia ( ) 15, 1735Leukemia ( -1742

Piceatannol, Natural Polyphenolic Stilbene, Inhibits Adipogenesis via Modulation of Mitotic Clonal Expansion and Insulin Receptor-dependent Insulin Signaling in Early Phase of Differentiation

“…2D). Piceatannol has been shown to inhibit cell viability and to induce apoptosis in various cell types such as macrophages (42), prostate cancer cells (43), adrenal pheochromocytoma cells (44), lymphoblasts (45), and neutrophils (46). However, our result showed that the viability of the differentiating 3T3-L1 cells was not significantly influenced by piceatannol treatment up to concentration of 100 M (Fig.…”

TEL-Syk fusion constitutively activates PI3-K/Akt, MAPK and JAK2-independent STAT5 signal pathways

“…Piceatannol not only inhibits protein tyrosine kinase Syk but also interferes with other kinases and induces apoptosis in leukemic lymphoblasts. 66,67 TEL-Syk fusion is a useful tool in the search for another Syk-specific inhibitor and for future investigation of Syk.…”

Induction of apoptosis by enediyne antibiotic calicheamicin ϑII proceeds through a caspase-mediated mitochondrial amplification loop in an entirely Bax-dependent manner

“…Mitochondrial apoptosis is the most prominent intrinsic apoptosis signalling pathway (for reviews, see, Calicheamicin activates mitochondria via caspases and Bax A Prokop et al Kroemer and Reed, 2000;Martinou and Green, 2001). It is triggered by various cytotoxic drugs such as taxol or epirubicin (Wieder et al, 2001a;von Haefen et al, 2003), natural compounds such as piceatannol (Wieder et al, 2001b), truncated ceramides or ionizing radiation . In a first series of experiments, we demonstrated that challenge with calicheamicin led to a dramatic decrease of the mitochondrial membrane potential, which was observed in approximately 80% of BJAB cells.…”

“…In addition, the apoptotic program may be triggered by various, unphysiological death stimuli, for example, ionizing radiation , chemotherapeutic anticancer drugs (Engels et al, 2000;Wieder et al, 2001a) and by natural compounds (Wieder et al, 2001b). So far, three major pathways of apoptotic cell death have been defined: (i) the death receptor-mediated signalling cascade , (ii) the mitochondrial pathway involving the apoptosome (Daniel, 2000;Rudner et al, 2001), and (iii) the endoplasmic reticulum-dependent stress response (Belka and Budach, 2002;Rudner et al, 2002).…”