Resveratrol, an antioxidant present in red wine, induces apoptosis in human promyelocytic leukemia (HL-60) cells

Surh, Young Joon; Hurh, Yeon Jin; Kang, Jee Young; Lee, Eunyong; Lee, Su Jeen

doi:10.1016/s0304-3835(99)00039-7

Cited by 304 publications

(203 citation statements)

References 32 publications

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“…In addition, internucleosomal DNA fragmentation as determined by agarose gel electrophoresis and kinetic analysis of cell cycle distribution by flow cytometry also clearly revealed that resveratrol and its derivatives rapidly induced apoptotic cell death. Previous studies showed the apoptotic effects of resveratrol in HL-60 cells (Surh et al, 1999;Joe et al, 2002) and in melanoma cells (Niles et al, 2003), and vaticanol C, a resveratrol tetramer, in colon cancer cell lines (Ito et al, 2002). Howerver, the present study is the first demonstration of resveratrol dimers and trimers-induced potent apoptotic HL-60 cell death.…”

Section: Discussionmentioning

confidence: 50%

“…Resveratrol has been reported to block the S-G2 transition and arrest the S phase of the cell cycle in HL-60 cells (Ragione et al, 1998;Joe et al, 2002). The present study showed a gradual reduction in the proportion of cell cycle in the G1, S and G2/M phases with concomitant increase in the percentage of sub-G1 phase as reported by Surh et al (1999). Since concentrations required for resveratrol to induce apoptosis were often higher than those that induced GAPDH cell cycle arrest, we might not observe the arrest in the S-phase prior to apoptosis.…”

Section: Discussionmentioning

confidence: 53%

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Resveratrol derivatives potently induce apoptosis in human promyelocytic leukemia cells

Kang

Park²,

Choi³

et al. 2003

Exp Mol Med

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 53%

Resveratrol derivatives potently induce apoptosis in human promyelocytic leukemia cells

Kang

Park²,

Choi³

et al. 2003

Exp Mol Med

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“…Our results also agree with previous data showing that RES decreased Bcl-2 levels in human promyelocytic leukemia HL-60 cells. 49 RES also affected the activity of the Bcl-2 regulator NF-kB. EMSA experiments showed significant downregulation in the binding of p65(RelA)/p50 to DNA at concentrations of RES that induce apoptosis.…”

Section: Discussionmentioning

confidence: 96%

Resveratrol‐induced apoptosis in MCF‐7 human breast cancer cells involves a caspase‐independent mechanism with downregulation of Bcl‐2 and NF‐κB

Pozo‐Guisado

Merino

Mulero‐Navarro

et al. 2005

Intl Journal of Cancer

209

143

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Resveratrol (RES), a chemopreventive molecule, inhibits the proliferation of tumor cells of different etiologies. We previously showed that RES alters the cell cycle and induces apoptosis in MCF-7 breast tumor cells by interfering with the estrogen receptor (ERa)-dependent phosphoinositide 3-kinase (PI3K) pathway. Here, we analyzed signaling downstream of PI3K, to understand the mechanisms of RES-induced apoptosis. Apoptotic death by RES in MCF-7 was mediated by Bcl-2 downregulation since overexpression of this protein abolished apoptosis. Decreased Bcl-2 levels were not related to cytochrome c release, activation of caspases 3/8 or poly(ADP-ribose) polymerase proteolysis. However, RES decreased mitochondrial membrane potential and increased reactive oxygen species and nitric oxide production. NF-kB, a regulator of Bcl-2 expression, and calpain protease activity, a regulator of NF-kB, were both inhibited by RES. The patterns for NFkB and calpain activities followed that of PI3K and were inhibited by LY294002. NF-kB inhibition coincided with diminished MMP-9 activity and cell migration. These data suggest that RES-induced apoptosis in MCF-7 could involve an oxidative, caspase-independent mechanism, whereby inhibition of PI3K signaling converges to Bcl-2 through NF-kB and calpain protease activity. Therefore, Bcl-2 and NF-kB could be considered potential targets for the chemopreventive activity of RES in estrogen-responsive tumor cells. ' 2005 Wiley-Liss, Inc.Key words: resveratrol; caspase; Bcl-2; NF-kB; apoptosis Among natural compounds with beneficial effects on human health, RES (3,4 0 ,5-trihydroxystilbene) has attracted considerable interest. This molecule, present at relevant concentrations in red wine, 1 has been associated with a lower incidence of cardiovascular disease. Different studies have also suggested a beneficial effect of RES in cancer since it inhibits proliferation and promotes death in tumor cell lines of different origins, 2-4 and, in vivo, suppresses the formation of skin 5 and mammary gland 6 tumors in rodent models of carcinogenesis.We, as well as other laboratories, have found that the ability of RES to inhibit cell viability and proliferation in the human breast cancer cell lines MCF-7 and MDA-MB-231 was unrelated to ERa status. 7,8 However, apoptotic cell death was present only in ERapositive MCF-7 and involved cell-specific regulation of the G 1 /S and G 2 /M transitions of the cell cycle. 2,8 RES properties are related to ERa since this compound has estrogenic or antiestrogenic activities depending on its concentration and the phenotype of the target cell. 9,10 ERa, in addition to its nuclear role as a transcription factor, is involved in regulating the PI3K pathway, which controls cell growth, proliferation and apoptosis. [11][12][13] In MCF-7 cells, RES induced a biphasic pattern of PI3K activity that increased at low concentrations and decreased at high concentrations. Activation of downstream PI3K effectors PKB/AKT and GSK-3 closely followed the pattern of PI3K activity. 14 The ...

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“…[22][23][24][25] Resveratrol, an antioxidant found in the skin of grapes, especially red grapes, has been shown, in in vitro and in vivo studies, to affect initiation, promotion, and progression of different cancers, including leukemia. [26][27][28] Different mechanistic pathways have been proposed for its antileukemic effect including induction of leukemia cell differentiation, apoptosis, cell cycle arrest, and inhibition of DNA synthesis. 29,30 The low in vivo toxicity of this compound would indicate that further research is warranted to determine its potential as an antileukemia agent.…”

Section: Discussionmentioning

confidence: 99%

Risk factors of myelodysplastic syndromes: a case–control study

et al. 2005

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Resveratrol, an antioxidant present in red wine, induces apoptosis in human promyelocytic leukemia (HL-60) cells

Cited by 304 publications

References 32 publications

Resveratrol derivatives potently induce apoptosis in human promyelocytic leukemia cells

Resveratrol derivatives potently induce apoptosis in human promyelocytic leukemia cells

Resveratrol‐induced apoptosis in MCF‐7 human breast cancer cells involves a caspase‐independent mechanism with downregulation of Bcl‐2 and NF‐κB

Risk factors of myelodysplastic syndromes: a case–control study

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