A dietary anthocyanidin delphinidin induces apoptosis of human prostate cancer PC3 cells in vitro and in vivo : involvement of nuclear factor-kappaB signaling
Delphinidin, a major anthocyanidin present in many pigmented fruits and vegetables, possesses antioxidant, anti-inflammatory, and antiangiogenic properties. In this study, we provide evidence that it could be developed as a novel agent against human prostate cancer (PCa). We observed that delphinidin treatment to human PCa LNCaP, C4-2, 22Rnu1, and PC3 cells resulted in a dose-dependent inhibition of cell growth without having any substantial effect on normal human prostate epithelial cells. We selected PC3 cells as a test model system because of their highly aggressive proliferative nature. Delphinidin treatment of cells resulted in a dose-dependent induction of apoptosis and arrest of cells in G(2)-M phase. This induction of apoptosis seems to be mediated via activation of caspases because N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluromethylketone significantly reduced apoptosis induced by delphinidin. We also observed that delphinidin treatment of cells resulted in a dose-dependent decrease in (a) phosphorylation of IkappaB kinase gamma (NEMO), (b) phosphorylation of nuclear factor-kappaB (NF-kappaB) inhibitory protein IkappaBalpha, (c) phosphorylation of NF-kappaB/p65 at Ser(536) and NF-kappaB/p50 at Ser(529), (d) NF-kappaB/p65 nuclear translocation, and (e) NF-kappaB DNA binding activity. Delphinidin administration (2 mg, i.p. thrice weekly) to athymic nude mice implanted with PC3 cells resulted in a significant inhibition of tumor growth. Analysis of tumors from delphinidin-treated mice showed significant decrease in the expression of NF-kappaB/p65, Bcl2, Ki67, and PCNA. Taken together, our data suggest that delphinidin could be developed as an agent against human PCa.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2008 |
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| Erschienen: |
2008 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:68 |
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| Enthalten in: |
Cancer research - 68(2008), 20 vom: 15. Okt., Seite 8564-72 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hafeez, Bilal Bin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.11.2008 Date Revised 23.02.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1158/0008-5472.CAN-08-2232 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM183695259 |
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| 100 | 1 | |a Hafeez, Bilal Bin |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A dietary anthocyanidin delphinidin induces apoptosis of human prostate cancer PC3 cells in vitro and in vivo |b involvement of nuclear factor-kappaB signaling |
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| 520 | |a Delphinidin, a major anthocyanidin present in many pigmented fruits and vegetables, possesses antioxidant, anti-inflammatory, and antiangiogenic properties. In this study, we provide evidence that it could be developed as a novel agent against human prostate cancer (PCa). We observed that delphinidin treatment to human PCa LNCaP, C4-2, 22Rnu1, and PC3 cells resulted in a dose-dependent inhibition of cell growth without having any substantial effect on normal human prostate epithelial cells. We selected PC3 cells as a test model system because of their highly aggressive proliferative nature. Delphinidin treatment of cells resulted in a dose-dependent induction of apoptosis and arrest of cells in G(2)-M phase. This induction of apoptosis seems to be mediated via activation of caspases because N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluromethylketone significantly reduced apoptosis induced by delphinidin. We also observed that delphinidin treatment of cells resulted in a dose-dependent decrease in (a) phosphorylation of IkappaB kinase gamma (NEMO), (b) phosphorylation of nuclear factor-kappaB (NF-kappaB) inhibitory protein IkappaBalpha, (c) phosphorylation of NF-kappaB/p65 at Ser(536) and NF-kappaB/p50 at Ser(529), (d) NF-kappaB/p65 nuclear translocation, and (e) NF-kappaB DNA binding activity. Delphinidin administration (2 mg, i.p. thrice weekly) to athymic nude mice implanted with PC3 cells resulted in a significant inhibition of tumor growth. Analysis of tumors from delphinidin-treated mice showed significant decrease in the expression of NF-kappaB/p65, Bcl2, Ki67, and PCNA. Taken together, our data suggest that delphinidin could be developed as an agent against human PCa | ||
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| 700 | 1 | |a Siddiqui, Imtiaz Ahmad |e verfasserin |4 aut | |
| 700 | 1 | |a Asim, Mohammad |e verfasserin |4 aut | |
| 700 | 1 | |a Malik, Arshi |e verfasserin |4 aut | |
| 700 | 1 | |a Afaq, Farrukh |e verfasserin |4 aut | |
| 700 | 1 | |a Adhami, Vaqar Mustafa |e verfasserin |4 aut | |
| 700 | 1 | |a Saleem, Mohammad |e verfasserin |4 aut | |
| 700 | 1 | |a Din, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Mukhtar, Hasan |e verfasserin |4 aut | |
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