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Delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis, by inducing DR5 and causing caspase-mediated HDAC3 cleavage.

Ko H, Jeong MH, Jeon H, Sung GJ, So Y, Kim I, Son J, Lee SW, Yoon HG, Choi KC - Oncotarget (2015)

Bottom Line: TRAIL-induced apoptosis in prostate cancer cells pretreated with delphinidin was dependent on death receptor 5 (DR5) and downstream cleavage of histone deacetylase 3 (HDAC3).In conclusion, delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis by inducing DR5, thus causing caspase-mediated HDAC3 cleavage.Our data reveal a potential way of chemoprevention of prostate cancer by enabling TRAIL-mediated apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, College of Medicine, Dankook University, Seoul, South Korea.

ABSTRACT
TRAIL can induce apoptosis in some cancer cells and is an immune effector in the surveillance and elimination of developing tumors. Yes, some cancers are resistant to TRAIL. Delphinidin, a polyphenolic compound contained in brightly colored fruits and vegetables, has anti-inflammatory, anti-oxidant, and anti-tumorigenic activities. Here we showed that delphinidin sensitized TRAIL-resistant human prostate cancer cells to undergo apoptosis. Cells treated with delphinidin and TRAIL activated the extrinsic and intrinsic pathways of caspase activation. TRAIL-induced apoptosis in prostate cancer cells pretreated with delphinidin was dependent on death receptor 5 (DR5) and downstream cleavage of histone deacetylase 3 (HDAC3). In conclusion, delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis by inducing DR5, thus causing caspase-mediated HDAC3 cleavage. Our data reveal a potential way of chemoprevention of prostate cancer by enabling TRAIL-mediated apoptosis.

No MeSH data available.


Related in: MedlinePlus

Delphinidin sensitizes TRAIL-mediated apoptosis in human prostate cancer cells(A) The chemical structure of delphinidin. (B and C) Anti-proliferation effect of TRAIL in human prostate cancer cell lines. LNCaP (B) and Du145 cells (C) were treated with TRAIL in a dose- and time-dependent manner. LNCaP and Du145 cells were treated with different concentrations of TRAIL (0, 25, 50, 100, 150 ng/ml) for the indicated times (4, 8, 12 h) and cell viability was measured by MTT assay. The data are expressed as the mean ± SD for triplicates. (D) TRAIL induced apoptosis in prostate cancer cell lines. LNCaP and Du145 cells were treated with different concentration of TRAIL (0, 50, 100, 150 ng/ml) for 12 h. Cell viability was measured by a MTT assay.
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Figure 1: Delphinidin sensitizes TRAIL-mediated apoptosis in human prostate cancer cells(A) The chemical structure of delphinidin. (B and C) Anti-proliferation effect of TRAIL in human prostate cancer cell lines. LNCaP (B) and Du145 cells (C) were treated with TRAIL in a dose- and time-dependent manner. LNCaP and Du145 cells were treated with different concentrations of TRAIL (0, 25, 50, 100, 150 ng/ml) for the indicated times (4, 8, 12 h) and cell viability was measured by MTT assay. The data are expressed as the mean ± SD for triplicates. (D) TRAIL induced apoptosis in prostate cancer cell lines. LNCaP and Du145 cells were treated with different concentration of TRAIL (0, 50, 100, 150 ng/ml) for 12 h. Cell viability was measured by a MTT assay.

Mentions: LNCaP cells are more refractory to TRAIL-induced apoptosis than Du145 cells. Using the MTT assay and western blot analysis to assess PARP cleavage, we confirmed this differential sensitivity to the anti-proliferative effects and apoptosis in a dose- and time-dependent manner, respectively. As shown in Fig. 1B and 1C, TRAIL treatment for 12 h LNCaP cells were refractory to a TRAIL-induced anti-proliferative effect to a dose as high as 100 ng/ml, while treatments with 50 ng/ml TRAIL resulted in approximately 50% inhibition of cell growth in Du145 cells. Apoptosis was activated in both LNCap and Du145 cells upon treatment with 150 ng/ml and 50 ng/ml of TRAIL for 12 h, respectively, as confirmed by the results for PARP cleavage (Fig. 1D).


Delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis, by inducing DR5 and causing caspase-mediated HDAC3 cleavage.

Ko H, Jeong MH, Jeon H, Sung GJ, So Y, Kim I, Son J, Lee SW, Yoon HG, Choi KC - Oncotarget (2015)

Delphinidin sensitizes TRAIL-mediated apoptosis in human prostate cancer cells(A) The chemical structure of delphinidin. (B and C) Anti-proliferation effect of TRAIL in human prostate cancer cell lines. LNCaP (B) and Du145 cells (C) were treated with TRAIL in a dose- and time-dependent manner. LNCaP and Du145 cells were treated with different concentrations of TRAIL (0, 25, 50, 100, 150 ng/ml) for the indicated times (4, 8, 12 h) and cell viability was measured by MTT assay. The data are expressed as the mean ± SD for triplicates. (D) TRAIL induced apoptosis in prostate cancer cell lines. LNCaP and Du145 cells were treated with different concentration of TRAIL (0, 50, 100, 150 ng/ml) for 12 h. Cell viability was measured by a MTT assay.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4496411&req=5

Figure 1: Delphinidin sensitizes TRAIL-mediated apoptosis in human prostate cancer cells(A) The chemical structure of delphinidin. (B and C) Anti-proliferation effect of TRAIL in human prostate cancer cell lines. LNCaP (B) and Du145 cells (C) were treated with TRAIL in a dose- and time-dependent manner. LNCaP and Du145 cells were treated with different concentrations of TRAIL (0, 25, 50, 100, 150 ng/ml) for the indicated times (4, 8, 12 h) and cell viability was measured by MTT assay. The data are expressed as the mean ± SD for triplicates. (D) TRAIL induced apoptosis in prostate cancer cell lines. LNCaP and Du145 cells were treated with different concentration of TRAIL (0, 50, 100, 150 ng/ml) for 12 h. Cell viability was measured by a MTT assay.
Mentions: LNCaP cells are more refractory to TRAIL-induced apoptosis than Du145 cells. Using the MTT assay and western blot analysis to assess PARP cleavage, we confirmed this differential sensitivity to the anti-proliferative effects and apoptosis in a dose- and time-dependent manner, respectively. As shown in Fig. 1B and 1C, TRAIL treatment for 12 h LNCaP cells were refractory to a TRAIL-induced anti-proliferative effect to a dose as high as 100 ng/ml, while treatments with 50 ng/ml TRAIL resulted in approximately 50% inhibition of cell growth in Du145 cells. Apoptosis was activated in both LNCap and Du145 cells upon treatment with 150 ng/ml and 50 ng/ml of TRAIL for 12 h, respectively, as confirmed by the results for PARP cleavage (Fig. 1D).

Bottom Line: TRAIL-induced apoptosis in prostate cancer cells pretreated with delphinidin was dependent on death receptor 5 (DR5) and downstream cleavage of histone deacetylase 3 (HDAC3).In conclusion, delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis by inducing DR5, thus causing caspase-mediated HDAC3 cleavage.Our data reveal a potential way of chemoprevention of prostate cancer by enabling TRAIL-mediated apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, College of Medicine, Dankook University, Seoul, South Korea.

ABSTRACT
TRAIL can induce apoptosis in some cancer cells and is an immune effector in the surveillance and elimination of developing tumors. Yes, some cancers are resistant to TRAIL. Delphinidin, a polyphenolic compound contained in brightly colored fruits and vegetables, has anti-inflammatory, anti-oxidant, and anti-tumorigenic activities. Here we showed that delphinidin sensitized TRAIL-resistant human prostate cancer cells to undergo apoptosis. Cells treated with delphinidin and TRAIL activated the extrinsic and intrinsic pathways of caspase activation. TRAIL-induced apoptosis in prostate cancer cells pretreated with delphinidin was dependent on death receptor 5 (DR5) and downstream cleavage of histone deacetylase 3 (HDAC3). In conclusion, delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis by inducing DR5, thus causing caspase-mediated HDAC3 cleavage. Our data reveal a potential way of chemoprevention of prostate cancer by enabling TRAIL-mediated apoptosis.

No MeSH data available.


Related in: MedlinePlus