Resveratrol induces apoptosis in LNCaP cells and requires hydroxyl groups to decrease viability in LNCaP and DU 145 cells

Morris, Gary Z.; Williams, R. L.; Elliott, Martin; Beebe, Stephen J.

doi:10.1002/pros.10122

Cited by 43 publications

(17 citation statements)

References 39 publications

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“…It has been suggested that available hydroxyl groups are important for decreasing cancer cell viability. 9 Our results seem to agree to this hypothesis, in fact the compound 5-allyl-3-nitrobenzene-1,2-diol (3) was significantly more potent than eugenol (1).Necrosis results in a disruption of cytoplasmic membrane and the necrotic cells release cytoplasmic LDH and other cytotoxic substances into the medium. We therefore examined the membrane permeability of the treated cells through the existence of LDH in their culture medium.…”

supporting

confidence: 79%

Eugenol and its synthetic analogues inhibit cell growth of human cancer cells (Part I)

Cardile

Gallardo

Cardona

et al. 2008

J. Braz. Chem. Soc.

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Propriedades antioxidante e anticancerígena foram relatadas para o Eugenol (4-alil-2-metoxifenol) (1). Na tentativa de aumentar a atividade intrínseca deste composto natural, alguns derivados foram sintetizados. O eugenol foi extraído do óleo de cravo da Índia e seus análogos (2-6) foram obtidos por reações de acetilação e nitração. Eugenol (1) e seus análogos (2-6) foram avaliados in vitro frente a duas linhagens de células de câncer humanas: DU-145 (células de câncer de próstata, insensíveis a andrógeno) e KB (células de carcinoma escamoso oral). A viabilidade celular foi avaliada por ensaios com sal de tetrazólio. A liberação de desidrogenase lática (LDH) também foi investigada para avaliar a toxicidade celular como um resultado do rompimento celular subseqüente à ruptura da membrana. Todos os compostos apresentaram atividade inibitória sobre o crescimento das células cancerosas examinadas. Os resultados obtidos demonstram que os compostos 5-alil-3-nitrobenzeno-1,2-diol (3) e acetato de 4-alil-2-metoxi-5-nitrofenol (5) foram significativamente mais ativos que o eugenol (p < 0,001), com valores de IC 50 em células DU-145 de 19,02 × 10 -6 e 21,5 × 10 -6 mol L -1 respectivamente, sugerindo que a presença dos grupos nitro e hidroxila podem ser importantes na atividade destes compostos. Os resultados também parecem indicar que a morte por apoptose está sendo induzida em células KB e DU-145. Nas condições experimentais avaliadas, não foi observado qualquer aumento estatisticamente significativo na liberação de LDH pelas células de câncer quando tratadas com eugenol e seus análogos.Eugenol (4-allyl-2-methoxyphenol) (1) has been reported to possess antioxidant and anticancer properties. In an attempt to enhance intrinsic activity of this natural compound, some derivatives were synthesized. Eugenol was extracted from cloves oil and further, the eugenol analogues (2-6) were obtained through acetylation and nitration reactions. Eugenol (1) and its analogues (2-6) were examined by in vitro model of cancer using two human cancer cell lines: DU-145 (androgeninsensitive prostate cancer cells) and KB (oral squamous carcinoma cells). Cell viability, by tetrazolium salts assay, was measured. Lactic dehydrogenase (LDH) release was also investigated to evaluate the presence of cell toxicity as a result of cell disruption, subsequent to membrane rupture. In the examined cancer cells, all compounds showed cell-growth inhibition activity. The obtained results demonstrate that the compounds 5-allyl-3-nitrobenzene-1,2-diol (3) and 4-allyl-2-methoxy-5-nitrophenyl acetate (5) were significantly (p < 0,001) more active than eugenol, with IC 50 values in DU-145 cells of 19.02 x 10 -6 and 21.5 × 10 -6 mol L -1 , respectively, and in KB cells of 18.11 × 10 -6 and 21.26 × 10 -6 mol L -1 , respectively, suggesting that the presence of nitro and hydroxyl groups could be important in the activity of these compounds. In addition, our results seem to indicate that apoptotic cell demise appears to be induced in KB and DU-145 cells. In fact, in ou...

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supporting

confidence: 79%

Eugenol and its synthetic analogues inhibit cell growth of human cancer cells (Part I)

Cardile

Gallardo

Cardona

et al. 2008

J. Braz. Chem. Soc.

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“…Similar biological effects of resveratrol have been reported in the androgen-independent prostate cancer (DU145 or PC-3; refs. 5,10,35,36) and glioma (U251; ref. 37) cell lines, which harbor constitutively-active Stat3 (33,38).…”

Section: Discussionmentioning

confidence: 99%

“…36) or in parallel with modulation of other factors, such as prostate-specific antigen (5,6,49). Previous studies also indicate that resveratrol-mediated apoptosis of breast cancer and endometrial adenocarcinoma cells may be dependent or independent of the estrogen receptor status (2, 50 -52).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein

Kotha

Sekharam²,

Cilenti³

et al. 2006

Molecular Cancer Therapeutics

268

184

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Resveratrol is a naturally occurring phytoalexin with antioxidant and antiinflammatory properties. Recent studies suggest that resveratrol possesses anticancer effects, although its mechanism of action is not well understood. We now show that resveratrol inhibits Src tyrosine kinase activity and thereby blocks constitutive signal transducer and activator of transcription 3 (Stat3) protein activation in malignant cells. Analyses of resveratrol-treated malignant cells harboring constitutively-active Stat3 reveal irreversible cell cycle arrest of v-Src-transformed mouse fibroblasts (NIH3T3/v-Src), human breast (MDA-MB-231), pancreatic (Panc-1), and prostate carcinoma (DU145) cell lines at the G 0 -G 1 phase or at the S phase of human breast cancer (MDA-MB-468) and pancreatic cancer (Colo-357) cells, and loss of viability due to apoptosis. By contrast, cells treated with resveratrol, but lacking aberrant Stat3 activity, show reversible growth arrest and minimal loss of viability. Moreover, in malignant cells harboring constitutively-active Stat3, including human prostate cancer DU145 cells and v-Src-transformed mouse fibroblasts (NIH3T3/v-Src), resveratrol treatment represses Stat3-regulated cyclin D1 as well as Bcl-x L and Mcl-1 genes, suggesting that the antitumor cell activity of resveratrol is in part due to the blockade of Stat3-mediated dysregulation of growth and survival pathways. Our study is among the first to identify Src-Stat3 signaling as a target of resveratrol, further defining the mechanism of antitumor cell activity of resveratrol and raising its potential application in tumors with an activated Stat3 profile.

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“…Resveratrol has been shown to induce apoptotic cell death in a number of cancer cell lines, including hormonesensitive LNCaP prostate cells (15), hormone-insensitive DU 145 prostate cells (16), mouse myeloid leukemia cells (5), human B cell chronic leukemia cells (17), as well as several other human cancer cell lines such as MCF7, SW480, HCE7, Seg-1, and HL60 (2). Alteration of expression of Bcl-2 family of proteins, loss of mitochondrial function, release of cytochrome c, and activation of caspases may be involved in resveratrol-induced death, as shown in Bcl-2 overexpressing U937 cells (18), pancreatic carcinoma cells (19), mouse myeloid leukemia cells (5), normal and leukemic hematopoietic cells (17), and human Caco-2 colonic adenocarcinoma cells (20).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol-induced apoptotic death in human U251 glioma cells

Jiang

Zhang

Kuo

et al. 2005

Molecular Cancer Therapeutics

117

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Resveratrol (trans-3,4V,5-trihydroxystilbene) is a naturally occurring polyphenolic compound highly enriched in grapes, peanuts, red wine, and a variety of food sources. Resveratrol has antiinflammatory and antioxidant properties, and also has potent anticancer properties. Human glioma U251 cells were used to understand the molecular mechanisms by which resveratrol acts as an anticancer agent, since glioma is a particularly difficult cancer to treat and eradicate. Our data show that resveratrol induces dose-and time-dependent death of U251 cells, as measured by lactate dehydrogenase release and internucleosomal DNA fragmentation assays. Resveratrol induces activation of caspase-3 and increases the cleavage of the downstream caspase substrate, poly(ADP-ribose) polymerase. Resveratrol-induced DNA fragmentation can be completely blocked by either a general caspase inhibitor (Z-VAD-FMK) or a selective caspase-3 inhibitor (Z-DEVD-FMK), but not by a selective caspase-1 inhibitor. Resveratrol induces cytochrome c release from mitochondria to the cytoplasm and activation of caspase-9. Resveratrol also increases expression of proapoptotic Bax and its translocation to the mitochondria. Resveratrol inhibits U251 proliferation, as measured by MTS assay [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt], and induces G 0 /G 1 growth arrest, as determined by flow cytometry. The cyclin-dependent kinase inhibitor, olomoucine, prevents cell cycle progression and resveratrol-induced apoptosis. These results suggest that multiple signaling pathways may underlie the apoptotic death of U251 glioma induced by resveratrol, which warrants further exploration as an anticancer agent in human glioma. [Mol Cancer Ther 2005;4(4):554 -61]

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Resveratrol induces apoptosis in LNCaP cells and requires hydroxyl groups to decrease viability in LNCaP and DU 145 cells

Cited by 43 publications

References 39 publications

Eugenol and its synthetic analogues inhibit cell growth of human cancer cells (Part I)

Eugenol and its synthetic analogues inhibit cell growth of human cancer cells (Part I)

Resveratrol inhibits Src and Stat3 signaling and induces the apoptosis of malignant cells containing activated Stat3 protein

Resveratrol-induced apoptotic death in human U251 glioma cells

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