Differential response to zinc-induced apoptosis in benign prostate hyperplasia and prostate cancer cells☆

Yan, Michelle; Hardin, Karin; Ho, Emily

doi:10.1016/j.jnutbio.2009.04.002

Cited by 26 publications

(26 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was found that patients with diets rich in zinc exhibited reduced PCA mortality especially in patients with localized tumors [124]. Perhaps relatedly, exogenous zinc more potently inhibited the proliferation of benign prostatic hyperplasia cells (BPH-1) as compared to PC3 cells [125]. …”

Section: Prostate Cancer Chemopreventive Agentsmentioning

confidence: 99%

The strategies to control prostate cancer by chemoprevention approaches

Ting

Deep

Agarwal

et al. 2014

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

View full text Add to dashboard Cite

Prostate cancer (PCA) is the most commonly diagnosed cancer in men in the United States with growing worldwide incidence. Despite intensive investment in improving early detection, PCA often escapes timely detection and mortality remains high; this malignancy being the second highest cancer-associated mortality in American men. Collectively, health care costs of PCA results in an immense financial burden that is only expected to grow. Additionally, even in cases of successful treatment, PCA is associated with long-term and pervasive effects on patients. A proactive alternative to treating PCA is to prevent its occurrence and progression prior to symptomatic malignancy. This may serve to address the issue of burgeoning healthcare costs and increasing number of sufferers. One potential regimen in service of this alternative is PCA chemoprevention. Here, chemical compounds with cancer preventive efficacy are identified on the basis of their potential in a host of categories: their historical medicinal use, correlation with reduced risk in population studies, non-toxicity, their unique chemical properties, or their role in biological systems. PCA chemopreventive agents are drawn from multiple broad classes of chemicals, themselves further subdivided based on source or potential effect, with most derived from natural products. Many such compounds have shown efficacy, varying from inhibiting deregulated PCA cell signaling, proliferation, epithelial to mesenchymal transition (EMT), invasion, metastasis, tumor growth and angiogenesis and inducing apoptosis. Overall, these chemopreventive agents show great promise in PCA pre-clinical models, though additional work remains to be done in effectively translating these findings into clinical use.

show abstract

Section: Prostate Cancer Chemopreventive Agentsmentioning

confidence: 99%

The strategies to control prostate cancer by chemoprevention approaches

Ting

Deep

Agarwal

et al. 2014

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

View full text Add to dashboard Cite

show abstract

“… 13 Furthermore, the role of zinc in the development and progression of prostate cancer and its widespread antitumor efficacy have been shown in several malignancies. 14 – 17 Intracellular zinc status is associated with prostate carcinogenesis. For example, zinc deficiency contributes to tumor progression and development in cultured HRPC cells, 18 whereas increased levels of intracellular zinc decrease cancer cell proliferation and induce apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer

Koçdor¹,

Ateş²,

Aydın³

et al. 2015

DDDT

View full text Add to dashboard Cite

BackgroundExposure to exogenous zinc results in increased apoptosis, growth inhibition, and altered oxidative stress in cancer cells. Previous studies also suggested that zinc sensitizes some cancer cells to cytotoxic agents depending on the p53 status. Therefore, zinc supplementation may show anticancer efficacy solely and may increase docetaxel-induced cytotoxicity in non-small-cell lung cancer cells.MethodsHere, we report the effects of several concentrations of zinc combined with docetaxel on p53-wild-type (A549) and p53-null (H1299) cells. We evaluated cellular viability, apoptosis, and cell cycle progression as well as oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde levels.ResultsZinc reduced the viability of A549 cells and increased the apoptotic response in both cell lines in a dose-dependent manner. Zinc also amplified the docetaxel effects and reduced its inhibitory concentration 50 (IC50) values. The superoxide dismutase levels increased in all treatment groups; however, glutathione peroxidase was slightly increased in the combination treatments. Zinc also caused malondialdehyde elevations at 50 μM and 100 μM.ConclusionZinc has anticancer efficacy against non-small-cell lung cancer cells in the presence of functionally active p53 and enhances docetaxel efficacy in both p53-wild-type and p53-deficient cancer cells.

show abstract

“…4, 7 In fact, the concentration of fetal bovine serum (FBS) in the culture medium is an important factor affecting the zinc concentration to induce apoptosis, which is demonstrated to range from 15 μ M in the medium without FBS to 150 μ M in the medium with 10% FBS supplements. 38, 39, 40 Using the regular cell culture condition with 10% FBS, we observed that moderate zinc concentration (150 μ M) induces significant apoptosis by promoting p21 WAF1/Cip1 expression in both LNCaP and PC3 cells. Moreover, zinc-induced cell apoptosis or p21 WAF1/Cip1 augment were blocked by the chelating agents, which provided the evidence for the link between the reduction of intracellular zinc concentration and the development of prostate cancer.…”

Section: Discussionmentioning

confidence: 93%

PIAS1-modulated Smad2/4 complex activation is involved in zinc-induced cancer cell apoptosis

et al. 2013

View full text Add to dashboard Cite

Prostate cancer is one of the most frequently diagnosed cancers among men. Dietary intake of nutrients is considered crucial for preventing the initiation of events leading to the development of carcinoma. Many dietary compounds have been considered to contribute to cancer prevention including zinc, which has a pivotal role in modulating apoptosis. However, the mechanism for zinc-mediated prostate cancer chemoprevention remains enigmatic. In this study, we investigated the therapeutic effect of zinc in prostate cancer chemoprevention for the first time. Exposure to zinc induced apoptosis and resulted in transactivation of p21WAF1/Cip1 in a Smad-dependent and p53-independent manner in prostate cancer cells. Smad2 and PIAS1 proteins were significantly upregulated resulting in dramatically increased interactions between Smad2/4 and PIAS1 in the presence of zinc in LNCaP cells. Furthermore, it was found that the zinc-induced Smad4/2/PIAS1 transcriptional complex is responsible for Smad4 binding to SBE1 and SBE3 regions within the p21WAF1/Cip1 promoter. Exogenous expression of Smad2/4 and PIAS1 promotes zinc-induced apoptosis concomitant with Smad4 nuclear translocation, whereas endogenous Smad2/4 silencing inhibited zinc-induced apoptosis accompanying apparent p21WAF1/Cip1 reduction. Moreover, the knockdown of PIAS1 expression attenuated the zinc-induced recruitment of Smad4 on the p21WAF1/Cip1 promoter. The colony formation experiments demonstrate that PIAS1 and Smad2/4 silencing could attenuate zinc apoptotic effects, with a proliferation of promoting effects. We further demonstrate the correlation of apoptotic sensitivity to zinc and Smad4 and PIAS1 in multiple cancer cell lines, demonstrating that the important roles of PIAS1, Smad2, and Smad4 in zinc-induced cell death and p21WAF1/Cip1 transactivation were common biological events in different cancer cell lines. Our results suggest a new avenue for regulation of zinc-induced apoptosis, and provide a model that demonstrates zinc endorses the Smad2/4/PIAS1 complex to activate the p21WAF1/Cip1 gene that mediates apoptosis.

show abstract

Differential response to zinc-induced apoptosis in benign prostate hyperplasia and prostate cancer cells☆

Cited by 26 publications

References 44 publications

The strategies to control prostate cancer by chemoprevention approaches

The strategies to control prostate cancer by chemoprevention approaches

Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer

PIAS1-modulated Smad2/4 complex activation is involved in zinc-induced cancer cell apoptosis

Contact Info

Product

Resources

About

Differential response to zinc-induced apoptosis in benign prostate hyperplasia and prostate cancer cells☆

Cited by 26 publications

References 44 publications

The strategies to control prostate cancer by chemoprevention approaches

The strategies to control prostate cancer by chemoprevention approaches

Zinc supplementation induces apoptosis and&nbsp;enhances antitumor efficacy of docetaxel in&nbsp;non-small-cell lung cancer

PIAS1-modulated Smad2/4 complex activation is involved in zinc-induced cancer cell apoptosis

Contact Info

Product

Resources

About

Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer