Quercetin enhances TRAIL-induced apoptosis in prostate cancer cells via increased protein stability of death receptor 5

Jung, Young-Hwa; Heo, Jeonghoon; Lee, Yong J.; Kwon, Taeg Kyu; Kim, Young‐Ho

doi:10.1016/j.lfs.2010.01.008

Cited by 99 publications

(78 citation statements)

References 32 publications

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“…The expression of the death receptors and proapoptotic or antiapoptotic proteins in cancer cells is involved in TRAILresistance (1)(2)(3)(4)(5)(6)(7)(8). Studies of our group as well as of other researchers have shown that TRAIL-resistant cancer cells can be sensitized to TRAIL-mediated apoptosis by flavonoids (9)(10)(11)(12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 79%

The dietary flavonol fisetin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells

Szliszka

Helewski²,

Mizgała³

et al. 2011

Int J Oncol

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Abstract. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous agent that induces apoptosis selectively in cancer cells. Soluble or expressed in immune cells, TRAIL plays an important role in the defense against tumour cells. The resistance of cancer cells to TRAIL immune surveillance is implicated in tumour development. Naturally occurring flavonoids can sensitize TRAIL-resistant cancer cells and augment their apoptotic activity. Fisetin, a dietary flavonol has cancer preventive properties. This study was designed to investigate the effect of fisetin on the TRAILinduced apoptosis potential in prostate cancer cells. Prostate cancer cell lines represent an ideal model for research in chemoprevention. Cytotoxicity was measured by MTT and LDH assays. Apoptosis was detected using Αnnexin V-FITC by flow cytometry and fluorescence microscopy. Mitochondrial membrane potential (ΔΨm) was evaluated using DePsipher staining by fluorescence microscopy. Death receptor (TRAIL-R1 and TRAIL-R2) expression was analysed by flow cytometry. Inhibition of NF-κB (p65) activation was confirmed with an ELISA-based TransAM NF-κB kit. Caspase-8 and caspase-3 activities were determined by colorimetric protease assays. Our study demonstrates that fisetin sensitizes the TRAIL-resistant androgen-dependent LNCaP and the androgen-independent DU145 and PC3 prostate cancer cells to TRAIL-induced death. Fisetin augmented TRAIL-mediated cytotoxicity and apoptosis in prostate cancer LNCaP cells by engaging the extrinsic (receptor-mediated) and intrinsic (mitochondrial) apoptotic pathways. Fisetin increased the expression of TRAIL-R1 and decreased the activity of NF-κB. Co-treatment of cancer cells with TRAIL and fisetin caused significant activation of caspase-8 and caspase-3 and disruption of ΔΨm. Our data indicate the usefulness of fisetin in prostate cancer chemoprevention through enhancement of TRAIL-mediated apoptosis.

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Section: Introductionmentioning

confidence: 79%

The dietary flavonol fisetin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells

Szliszka

Helewski²,

Mizgała³

et al. 2011

Int J Oncol

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“…Brazilian propolis enhanced the sensitivity of LNCaP prostate cancer cells to TRAIL by the regulation of TrAIL-r2 expression. Dietary flavonoids, including apigenin, baicalein and quercetin have been shown to increase the expression of the DR, TRAIL-R2, on the surface of prostate cancer cells and to augment TRAIL-mediated apoptosis (6,9,12). In some cell lines, DR engagement of the extrinsic pathway is sufficient to induce apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Similar studies have described the synergistic apoptotic effect of TRAIL with naturally occurring polyphenols on cancer cells. Quercetin enhanced the TRAILmediated cytotoxicity by increasing TRAIL-R2 expression, activating caspases and decreasing the expression of the antiapoptotic serine/threonine kinase, Akt, or survivin in prostate cancer, lung cancer and hepatoma cells (12,(52)(53)(54)(55). kaempferol sensitized colon cancer cells through the upregulation of TRAIL-R2 expression (56).…”

Section: Discussionmentioning

confidence: 99%

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Ethanolic extract of Brazilian green propolis sensitizes prostate cancer cells to TRAIL-induced apoptosis

Szliszka

Zydowicz²,

Janoszka³

et al. 2011

Int J Oncol

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Abstract. Prostate cancer represents an ideal disease for chemopreventive intervention. Propolis possesses immunomodulatory, anti-tumour and chemopreventive properties. The tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is an important endogenous anti-cancer agent that induces apoptosis selectively in tumour cells. However, some cancer cells are resistant to TRAIL-mediated apoptosis. Naturally occurring phenolic and polyphenolic compounds sensitize TRAIL-resistant cancer cells and augment the apoptotic activity of TRAIL. The ethanolic extract of Brazilian green propolis (EEP) is rich in phenolic components. Our in vitro results indicate the potential targets in the TRAILinduced apoptotic pathway for the cancer chemopreventive activity of Brazilian propolis. We examined the cytotoxic and apoptotic effects of Brazilian EEP and its bioactive components in combination with TRAIL on LNCaP prostate cancer cells. The chemical composition of Brazilian green propolis was determined by high performance liquid chromatographydiode array detection. The cytotoxicity was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl-tetrazolium and lactate dehydrogenase assays. Apoptosis was detected using annexin V-FITC by f low cytometry and f luorescence microscopy. The mitochondrial membrane potential (∆Ψm) was evaluated using DePsipher staining by fluorescence microscopy. Flow cytometry was used to analyse death receptor (TRAIL-R1 and TRAIL-R2) expression in LNCaP cells. The inhibition of nuclear factor-κB (NF-κB) (p65) activation in cancer cells was confirmed by the ELISA-based TransAM NF-κB kit. The LNCaP cells were shown to be resistant to TRAIL-induced apoptosis. Our study demonstrates that EEP sensitizes TRAIL-resistant prostate cancer cells. The main phenolic components detected in Brazilian green propolis are artepillin C, quercetin, kaempferol and p-coumaric acid. Brazilian propolis and its bioactive components markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells. Brazilian EEP enhanced the expression of TRAIL-R2 and the activity of NF-κB in LNCaP cells. The co-treatment of prostate cancer cells with 100 ng/ml TRAIL and 50 µg/ml EEP increased the percentage of apoptotic cells to 65.8±1.2% and caused a significant disruption of ∆Ψm in LNCaP cells. We show that Brazilian EEP helped cells overcome TRAIL resistance by engaging both intrinsic and extrinsic apoptotic pathways and regulating NF-κB activity.

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“…TRAIL triggers apoptosis by binding to its death receptors DR4 and DR5 [4,5], and activating both death receptor (extrinsic) and mitochondria (intrinsic) apoptosis pathways [6,7]. Ligation of DR4/DR5 by TRAIL results in the assembly of a death-inducing signaling complex (DISC), which contains adapter components such as Fas associated death domain (FADD) [8].…”

mentioning

confidence: 99%

Over-expressing CYLD augments antitumor activity of TRAIL by inhibiting the NF-κB survival signaling in lung cancer cells

Yx²,

Hf³

et al. 2012

neo

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The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in tumor cells. But studies have demonstrated that many tumor cells were resistant to TRAIL-induced apoptosis. CYLD is recognized as a negative regulator of nuclear factor-kappa B (NF-κB) activity. To explore a correlation between CYLD expression and responsiveness to TRAIL in lung cancer cell lines, we established lung cancer cell lines that stably express CYLD. Our data provided the first evidence that increased expression of CYLD directly blocks TRAIL-induced NF-κB activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. CYLD may act as a therapeutic target of lung cancer. Targeting CYLD, in combination with TRAIL, may be a new strategy to treat lung cancer with high NF-κB activity.

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Quercetin enhances TRAIL-induced apoptosis in prostate cancer cells via increased protein stability of death receptor 5

Cited by 99 publications

References 32 publications

The dietary flavonol fisetin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells

The dietary flavonol fisetin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells

Ethanolic extract of Brazilian green propolis sensitizes prostate cancer cells to TRAIL-induced apoptosis

Over-expressing CYLD augments antitumor activity of TRAIL by inhibiting the NF-κB survival signaling in lung cancer cells

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