A Dietary Anthocyanidin Delphinidin Induces Apoptosis of Human Prostate Cancer PC3 Cells In vitro and In vivo: Involvement of Nuclear Factor-κB Signaling

Abstract

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, 22Rν1, 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 G2-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 IκB kinase γ (NEMO), (b) phosphorylation of nuclear factor-κB (NF-κB) inhibitory protein IκBα, (c) phosphorylation of NF-κB/p65 at Ser536 and NF-κB/p50 at Ser529, (d) NF-κB/p65 nuclear translocation, and (e) NF-κB 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-κB/p65, Bcl2, Ki67, and PCNA. Taken together, our data suggest that delphinidin could be developed as an agent against human PCa.

Antioxidant Activities of Chokeberry Extracts and the Cytotoxic Action of Their Anthocyanin Fraction on HeLa Human Cervical Tumor Cells

“…6,7 These berries, because of their high content in anthocyanins, are being studied also for their ability to protect against oral, 8 colon, 9,10 breast, 8 and prostate 11,12 cancer. The objectives of this study were (1) to determine the contents of total flavonoids, procyanidins, anthocyanins, and polyphenols of chokeberry extracts obtained from three cultivars and to characterize their anthocyanin fraction by high-performance liquid chromatography (HPLC) analysis, (2) to measure and compare the antioxidant activity using three different single electron transfer (SET)-based assays [2,2 0 -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and cupric ion reducing antioxidant capacity (CUPRAC)], one hydrogen atom transfer (HAT)-based method (oxygen radical absorbance capacity [ORAC]), and the H 2 O 2 scavenging potential (HPS) assay, and (3) to evaluate the cytotoxic action and the pro-oxidative effect of the anthocyanin fraction on the HeLa tumor cervical cell line.…”

Induction of apoptosis in human colon cancer HCT-116 cells by anthocyanins through suppression of Akt and activation of p38-MAPK

“…The fruit has traditionally been used in Korean folk medicine for the treatment of inflammatory disorders and cancer. The intense dark red hue reflects an abundance of anthocyanin pigments the anti-cancer activities of which have been reported in vitro and in vivo (4)(5)(6). Therefore, we postulated that the anthocyanins are major components for the anti-cancer activities of the Meoru.…”

Zac1 is a histone acetylation-regulated NF-κB suppressor that mediates histone deacetylase inhibitor-induced apoptosis

“…The phosphorylation levels of these two sites are dramatically increased upon stimulation of NF-kB activity. 29,30 Moreover, studies show that tumor cell apoptosis induced by anticancer reagents is associated with decreased p65 phosphorylation at Ser536 residue, [31][32][33] suggesting that p65 Ser536 phosphorylation is important for maintaining cancer cell survival and can be inhibited by anticancer reagents. In this study we showed that not only phosphorylation of Ser536 but also phosphorylation of Ser468 is downregulated during HDAC inhibitor-induced apoptosis of EC cells.…”