Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis

Siddiqui, Imtiaz A.; Malik, Arshi; Adhami, Vaqar M.; Asim, Mohammad; Hafeez, Bilal Bin; Sarfaraz, Sami; Mukhtar, Hasan

doi:10.1038/sj.onc.1210840

Cited by 201 publications

(163 citation statements)

References 34 publications

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“…However, it has also been shown that numerous TRAIL-resistant cancer cells exist (7). Therefore, a number of approaches, such as combined administration of TRAIL with various sensitizers, including synthetic small molecules, natural compounds and enzyme inhibitors, are currently being tested in attempt to overcome TRAIL resistance (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells

et al. 2017

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Abstract. Andrographolide, a natural compound isolated from Andrographis paniculata, has been reported to possess antitumor activity. In the present study, the effect of andrographolide in human gastric cancer (GC) cells was investigated. Andrographolide induced cell death with apoptotic and non-apoptotic features. At a low concentration, andrographolide potentiated apoptosis and reduction of clonogenicity triggered by recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL). Exposure of GC cells to andrographolide altered the expression level of several growth-inhibiting and apoptosis-regulating proteins, including death receptors. It was demonstrated that activity of the TRAIL-R2 (DR5) pathway was critical in the development of andrographolide-mediated rhTRAIL sensitization, since its inhibition significantly reduced the extent of apoptosis induced by the combination of rhTRAIL and andrographolide. In addition, andrographolide increased reactive oxygen species (ROS) generation in a dose-dependent manner. N-acetyl cysteine prevented andrographolide-mediated DR5 induction and the apoptotic effect induced by the combination of rhTRAIL and andrographolide. Collectively, the present study demonstrated that andrographolide enhances TRAIL-induced apoptosis through induction of DR5 expression. This effect appears to involve ROS generation in GCs.

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Section: Introductionmentioning

confidence: 99%

Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells

et al. 2017

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“…[1][2][3][4][5][6] Within the PCa-derived cell lines studied, androgen-independent PC3 cells are previously shown to be moderately sensitive, and LNCaP cells are reported to be resistant to TRAIL-induced apoptosis. [11][12][13][14][15][16][17][18][19][20] Given the established role of ethanol in inducing cell death, it is a promising agent for promoting tumor cell death in combination with known therapeutic drugs such as TRAIL. Indeed, a critical role for ethanol in promoting apoptotic events in various cell lines and animal models has been well documented.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9] Interestingly, resistance to TRAIL by PCa cells can be overcome when TRAIL is combined with various chemotherapeutic agents. [10][11][12][13][14][15][16][17][18][19] Ethanol-induced apoptotic cell death has been well recognized in many cell types and animal models. [20][21][22][23][24] High concentrations of ethanol can effectively destroy hepatoma tumor as well as normal cells, whereas lower concentrations of ethanol selectively induces apoptosis in hepatoma tumor cells but not in normal hepatocytes.…”

Section: Introductionmentioning

confidence: 99%

Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand through induction of reactive oxygen species in prostate cancer cells

Plante

Arscott

Folsom

et al. 2012

Prostate Cancer Prostatic Dis

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BACKGROUND: Effective treatment of prostate cancer (PCa) remains a major challenge due to chemoresistance to drugs including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Ethanol and ethanol extracts are known apoptosis inducers. However, cytotoxic effects of ethanol on PCa cells are unclear. METHODS: In this study we utilized PC3 and LNCaP cell culture models. We used immunohistochemical analysis, western blot analysis, reactive oxygen species (ROS) measurement, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) Cell Proliferation Assay, Annexin-V staining and flow cytometry for quantification of apoptosis. In vitro soft agar colony formation and Boyden chamber invasion assays were used. Tumorigenicity was measured in a xenotransplantation mouse model. RESULTS: Here, we demonstrate that ethanol enhances the apoptosis-inducing potential of TRAIL in androgen-resistant PC3 cells and sensitizes TRAIL-resistant, androgen sensitive LNCaP cells to apoptosis through caspase activation, and a complete cleavage of poly (ADP)-ribose polymerase, which was in association with increased production of ROS. The cytotoxicity of ethanol was suppressed by an antioxidant N-acetyl cystein pretreatment. Furthermore, ethanol in combination with TRAIL increased the expression of cyclin-dependent kinase inhibitor p21 and decreased the levels of Bcl-2 and phosphorylated-AKT. These molecular changes were accompanied by decreased proliferation, anchorage-independent growth and invasive potential of PC3 and LNCaP cells. In vivo studies using a xenotransplantation mouse model with PC3 cells demonstrated significantly increased apoptosis in tumors treated with ethanol and TRAIL in combination. CONCLUSIONS: Taken together, use of ethanol in combination with TRAIL may be an effective strategy to augment sensitivity to TRAIL-induced apoptosis in PCa cells.

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“…GTC-induced inhibition of proteasome activity, however, has not been directly confirmed in rodent models or human studies.Another study by Mitterberger et al (2007) showed that tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) is a part of the extrinsic pathway of apoptosis and this death receptor pathway is often resistant in the androgen sensitive LNCaP cells (Sanlioglu et al, 2007). Recently, a synergistic effect of EGCG (20 μM) when used in combination with TRAIL (100 ng/ml) was observed and resulted in three events: upregulation of poly(ADP-ribose) polymerase cleavage and modulation of pro-and anti-apoptotic Bcl-2 family of proteins, modulation of TRAIL R1 and Fas-associated death domain and FLICE-inhibitory protein proteins leading to decreased invasion and migration of LNCaP cells (Siddiqui et al, 2008). Further evaluation of EGCG in combination with TRAIL revealed decreased invasion and migration as seen through inhibition of VEGF, uPA, angiopoieetin 1 and 2, MMP2,-3, -9 and upregulation of TIMP-1.…”

Section: Prostate Cancermentioning

confidence: 99%

Green tea mechanism of action in fighting different types of cancer

2016

Sci. Agric

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Eat and drink natural to fight cancer. Natural products are important therapeutic effects with low toxicity, and could be used in cancer chemoprevention. This is the most important healthy lifestyle behaviors in the 21 century. More than half patients use vitamins or herbs concurrently with conventional anticancer treatment. Flavonoids or polyphenols existing in vegetables, fruits and beverages are known by their antioxidant properties and considered as anti-cancer agents. Examples of these include green tea. Green tea composed of flavonoid compounds with phenolic structures. These phytochemicals are highly reactive with other compounds, such as reactive oxygen species and biologic macromolecules, to neutralize free radicals or initiate biological effects. Phenolic phytochemicals with promising properties to benefit human health includes a group of polyphenol compounds, called catechins, found in green tea. This article summarizes the findings of studies using green tea polyphenols as chemopreventive and discusses the possible mechanisms of action in fighting different types of cancer.

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Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis

Cited by 201 publications

References 34 publications

Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells

Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells

Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand through induction of reactive oxygen species in prostate cancer cells

Green tea mechanism of action in fighting different types of cancer

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