HIF‐1α promotes survival of prostate cells at a high zinc environment

Park, Sook Eun; Park, Jong-Wan; Cho, Young Suk; Ryu, Ji Hye; Paick, Jae Seung; Chun, Yang Sook

doi:10.1002/pros.20641

Cited by 24 publications

(19 citation statements)

References 38 publications

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“…The sections were deparaffinized, rehydrated through a graded alcohol series and heated in 10 mM sodium citrate (pH 6.0) for 5 min in a microwave to retrieve the antigens. Nonspecific sites were blocked with a solution containing 2.5% bovine serum albumin (SigmaAldrich) and 2% normal rabbit serum in PBS (pH 7.4) for 1 h, and the sections were then incubated overnight at 4°C with anti-HIF-1α (Santa Cruz) or anti-PCNA (Santa Cruz) antibody diluted 1:100 in blocking solution [17]. As negative controls, sections were incubated in blocking solution without primary antibody.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Vitamin C supplementation prevents testosterone-induced hyperplasia of rat prostate by down-regulating HIF-1α

Ryu

Park

et al. 2010

The Journal of Nutritional Biochemistry

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Section: Immunohistochemistrymentioning

confidence: 99%

Vitamin C supplementation prevents testosterone-induced hyperplasia of rat prostate by down-regulating HIF-1α

Ryu

Park

et al. 2010

The Journal of Nutritional Biochemistry

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“…This leads to the possibility that in the natural environment of the prostate gland, the normal glandular epithelial cells may incorporate increased Bcl-2 production and/or antiapoptotic responses, which could prevent the potential apoptotic cytotoxic effect of zinc. The report of Park et al provided evidence for a protective effect of increased HIF1α against cytotoxicity resulting from high zinc levels in prostate cells [32]. Pursuant studies identified the anti-apoptogenic agent, survivin, as a mediator of HIF1α protection of prostate cells from zinc cytotoxicity [33].…”

Section: Factors and Conditions That Protect Cells From The Cytotoxic Ementioning

confidence: 99%

Cytotoxic/tumor suppressor role of zinc for the treatment of cancer: an enigma and an opportunity

Costello

Franklin

2012

Expert Review of Anticancer Therapy

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A major issue relating to many cancers is the absence of effective chemotherapeutic agents; so that most often untreatable morbidity and death are prevalent once the cancer has been detected and has advanced. The search for efficacious anticancer agents is imperative. One potential agent is zinc, which is decreased in the development of some cancers in order to avoid its cytotoxic/tumor suppressor effects on the malignant cells. This provides the basis and opportunity to employ a treatment regimen that restores elevated zinc levels in the malignant cells and elicits the cytotoxic/tumor suppressor effects of zinc. The enigma is that this approach and expectation has not reached fruition. The question is “why?”. This article provides a discussion of relevant zinc issues that need to be considered and resolved. Important areas of research are identified as being essential for the successful application of zinc cytotoxicity/tumor suppression actions for the treatment of specific cancers.

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“…In fact, we previously reported the HIF-1α-inducing activity of Py-Zn in various cell lines, such as PC3, DU145, MKN28, and HEK293 cells [15]. In that study, we used Py-Zn as a zinc ionophore to transport Zn 2＋ into cells.…”

Section: Discussionmentioning

confidence: 99%

“…Given the previous reports, we tested four compounds as HIF-1α inducer candidates, namely, bafilomycin A1 [12], baicalein [13], EGCG [14], and Py-Zn [15]. The molecular structures of the test compounds are illustrated in Fig.…”

Section: Test Compoundsmentioning

confidence: 99%

Pyrithione-zinc Prevents UVB-induced Epidermal Hyperplasia by Inducing HIF-1α

Cho

Lee

Park

2010

Korean J Physiol Pharmacol

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Hippel-Lindau tumor suppressor protein; IRES, internal ribosome entry site; 5'-UTR, 5'-untranslated region; PI3K, phosphoinositide-3-kinase; mTOR, mammalian target of rapamycin; Akt, serine/threonine protein kinase; HSP, heat shock protein; MEK/ERK, mitogen-activated protein kinase kinase/extracellular signal-regulated kinase; HEK293, human embryonic kidney cell line 293; OTC, over-the-counter. Epidermal keratinocytes overgrow in response to ultraviolet-B (UVB), which may be associated with skin photoaging and cancer development. Recently, we found that HIF-1α controls the keratinocyte cell cycle and thereby contributes to epidermal homeostasis. A further study demonstrated that HIF-1α is down-regulated by UVB and that this process is involved in UVB-induced skin hyperplasia. Therefore, we hypothesized that the forced expression of HIF-1α in keratinocytes would prevent UVB-induced keratinocyte overgrowth. Among several agents known to induce HIF-1α , pyrithione-zinc (Py-Zn) overcame the UVB suppression of HIF-1α in cultured keratinocytes. Mechanistically, Py-Zn blocked the degradation of HIF-1α protein in keratinocytes, while it did not affect the synthesis of HIF-1α . Moreover, the p21 cell cycle inhibitor was down-regulated after UVB exposure, but was robustly induced by Py-Zn. In mice repeatedly irradiated with UVB, the epidermis became hyperplastic and HIF-1α disappeared from nuclei of epidermal keratinocytes. However, a cream containing Py-Zn effectively prevented the skin thickening and up-regulated HIF-1α to the normal level. These results suggest that Py-Zn is a potential agent to prevent UVB-induced photoaging and skin cancer development. This work also provides insight into a molecular target for treatment of UVB-induced skin diseases. Pyrithione-zinc Prevents UVB-induced Epidermal Hyperplasia by

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HIF‐1α promotes survival of prostate cells at a high zinc environment

Abstract: These results suggest that HIF-1alpha functions as an intrinsic defense molecule that enables prostate cells to survive in a zinc-rich environment.

Cited by 24 publications

References 38 publications

Vitamin C supplementation prevents testosterone-induced hyperplasia of rat prostate by down-regulating HIF-1α

Vitamin C supplementation prevents testosterone-induced hyperplasia of rat prostate by down-regulating HIF-1α

Cytotoxic/tumor suppressor role of zinc for the treatment of cancer: an enigma and an opportunity

Pyrithione-zinc Prevents UVB-induced Epidermal Hyperplasia by Inducing HIF-1α

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