Sensitization of TRAIL-resistant LNCaP cells by resveratrol (3, 4', 5 tri-hydroxystilbene): molecular mechanisms and therapeutic potential

Shankar, Sharmila; Chen, Qinghe; Siddiqui, Imtiaz A.; Sarva, Krishna; Srivastava, Rakesh K.

doi:10.1186/1750-2187-2-7

Cited by 89 publications

(74 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, some tumour cells are resistant to TRAIL-mediated cytotoxicity (19). Previously we and others have demonstrated that the LNCaP cell line is resistant to TRAIL-induced apoptosis (7,10,11,13,14,16,31,35,40). The recombinant human TRAIL used in this study is a soluble protein based on a natural ligand (13,34).…”

Section: Discussionmentioning

confidence: 99%

“…Dysregulated apoptotic pathways are significant in the initiation and progression of prostate cancer (4,7,17,39). The data accumulated from in vitro and in vivo studies suggest that TRAIL plays an important role in the maintenance of immune homeostasis, host tumour surveillance and defence against cancer cells (15)(16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

“…A similar observation was described by Siddiqui et al and Shankar et al in their in vitro studies with epigallocatechin-3-gallate (EGCG), resveratrol and curcumin. Resveratrol, a main compound found in red wine, curcumin (the active component of the spice turmeric derived from the rhizome of Curcuma longa) and EGCG (a green tea polyphenol), all helped LNCaP cells overcome TRAIL resistance through the upregulation of the DRs, TRAIL-R1 and/or TRAIL-R2, and caused a decrease in the ∆Ψm in prostate cancer cells (7,10,35). They reported that the sensitization of TRAIL-resistant LNCaP cells to TRAIL-induced apoptosis by bioactive agents is performed via the regulation of both the intrinsic and extrinsic apoptotic pathways.…”

Section: Discussionmentioning

confidence: 99%

“…The cells were incubated with 10 µl phycoerythrin-conjugated anti-TRAIL-R1 or anti-TRAIL-R2 monoclonal antibodies (r&D Systems) at 4˚c for 45 min. After staining, the cancer cells were washed with PBS and finally analyzed by flow cytometry (7,(35)(36)(37). The control consisted of cells in a separate tube treated with phycoerythrin-labeled mouse IgG 1 or mouse IgG 2B antibodies (r&D Systems).…”

Section: Flow Cytometric Analysis Of Dr Expression On the Cell Surfacementioning

confidence: 99%

“…The expression of the DRs, TRAIL-R1 or TRAIL-R2, and pro-apoptotic or anti-apoptotic proteins in cancer cells is involved in TRAIL-resistance (17)(18)(19). We and others have shown that TRAIL-resistant prostate cancer cells can be sensitized by bioactive polyphenols (7)(8)(9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Szliszka

Zydowicz²,

Janoszka³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Flow Cytometric Analysis Of Dr Expression On the Cell Surfacementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Szliszka

Zydowicz²,

Janoszka³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

show abstract

Resveratrol: Biological and pharmaceutical properties as anticancer molecule

Hsieh

2010

BioFactors

View full text Add to dashboard Cite

There is ample evidence that shows an inverse relationship between consumption of fruit/vegetable-rich diets and the risk of cancer at various anatomical sites. In this review, we will assess and summarize recent advances on cancer prevention by resveratrol, a natural stilbenoid present in red grapes, peanuts, some common drinks, and dietary supplements. We will focus on data published within the past few years on in vivo model tumor animal studies that reinforce the chemopreventive efficacy of resveratrol against a multitude of cancers, as well as on its sensitization/ enhancing activities against tumor cells when used in combination with established chemotherapeutic and pharmaceutical agents. In addition, we will review examples resveratrol-target proteins, denoted RTPs, including the 24-kDa cytosolic protein quinone reductase 2 (NQO2) discovered in our laboratory that may confer resveratrol responsiveness to cancer cells. We will discuss the possible role of NQO2 in mediating cancer prevention by resveratrol. Our analysis of published data strengthen support that resveratrol displays novel roles in various cellular processes, and help to establish an expanded molecular framework for cancer prevention by resveratrol in vivo.

show abstract

Development of drugs against hormone‐refractory prostate cancer

Kageyama

2008

Drug Development Research

View full text Add to dashboard Cite

The development of novel drugs for prostate cancer refractory to androgen deprivation therapy has been of great interest due to the lack of effective treatment modalities that can prolong the survival of such patients. The recent introduction of docetaxel-based combination chemotherapy has been a breakthrough with a modest, but significant, survival benefit. However, the improved survival period measured in months is far from ideal considering the non-negligible adverse events associated with docetaxel. Thus, numerous preclinical and clinical studies have been conducted to explore more favorable approaches to hormone-refractory prostate cancer. The novel agents under investigation include new chemotherapeutic drugs, drugs targeting signal transduction pathways, apoptosis modulators, drugs targeting the tumor microenvironment, molecular chaperone inhibitors, and dietary ingredients. Unfortunately, none of these agents have shown superior single-agent activity relative to docetaxel-based therapy to date. Therefore, developing the most effective combination therapies of new agents and docetaxel-based chemotherapy seems to be a reasonable approach until novel agents that can overcome the drug resistance of hormone-refractory prostate cancer cells emerge. Drug Dev Res 69 : 431-450, 2008.

show abstract

Sensitization of TRAIL-resistant LNCaP cells by resveratrol (3, 4', 5 tri-hydroxystilbene): molecular mechanisms and therapeutic potential

Cited by 89 publications

References 68 publications

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

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

Resveratrol: Biological and pharmaceutical properties as anticancer molecule

Development of drugs against hormone‐refractory prostate cancer

Contact Info

Product

Resources

About