Apoptosis is a Critical Cellular Event in Cancer Chemoprevention and Chemotherapy by Selenium Compounds

Sinha, Raghu; El‐Bayoumy, Karam

doi:10.2174/1568009043481614

Cited by 254 publications

(206 citation statements)

References 130 publications

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“…MSeA has been shown to be an effective anticancer agent in several in vitro and in vivo prostate cancer models and is known to induce growth arrest and apoptosis. 29,38,39 In our study, ex vivo MSeA treatment of PAIII cells resulted in significant reduction in the tumor weights in LW rats. More importantly, upon oral MSeA treatment, the number of metastatic lung foci was significantly reduced.…”

Section: Discussionsupporting

confidence: 51%

“…[22][23][24][25][26][27][28] The majority of the inhibitory effects of selenium compounds involve apoptosis as a critical event, and several effective organic selenium compounds including seleno-keto acids have been reviewed on the basis of their apoptotic potential in several cancer models including prostate cancer. 29,30 A promising anticancer agent methylseleninic acid (MSeA) has been shown to be effective in inhibiting prostate cancer growth in vitro and in TRAMP model. 31,32 However, the potential of MSeA as a therapeutic agent has not been tested in humans, and the underlying mechanism(s) of selenium compounds including MSeA have not been studied in hypoxic conditions.…”

mentioning

confidence: 99%

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Methylseleninic acid downregulates hypoxia‐inducible factor‐1α in invasive prostate cancer

Sinha

Null

Wolter

et al. 2011

Intl Journal of Cancer

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Alternative strategies are needed to control growth of advanced and hormone refractory prostate cancer. In this regard, we investigated the efficacy of methylseleninic acid (MSeA), a penultimate precursor to the highly reactive selenium metabolite, methylselenol, to inhibit growth of invasive and hormone refractory rat (PAIII) and human (PC-3 and PC-3M) prostate cancer cells. Our results demonstrate that MSeA inhibits PAIII cell growth in vitro as well as reduces weights of tumors generated by PAIII cells treated ex vivo. A significant reduction in the number of metastatic lung foci by MSeA treatment was also noted in Lobund-Wistar rats. The PAIII cells along with PC-3, DU145 and PC-3M cells undergo apoptosis after MSeA treatments in both normoxia and hypoxia. Treatment of metastatic rat and human prostate cancer cell lines with MSeA decreased hypoxiainducible factor-1a (HIF-1a) levels in a dose-dependent manner. Additionally, HIF-1a transcription activity both in normoxic and hypoxic conditions is reduced after MSeA treatment of prostate cancer cells. Furthermore, VEGF and GLUT1, downstream targets of HIF-1a, were also reduced in prostate cancer cells after MSeA treatment. Our study illustrates the efficacy of MSeA in controlling growth of hormone refractory prostate cancer by downregulating HIF-1a, which is possibly occurring through stabilization or increase in prolyl hydroxylase activity.In men with advanced prostate cancer, hormone therapy is accepted as the initial treatment of choice and produces good responses in most patients. However, many patients relapse and become resistant to further hormone manipulation. Radical prostatectomy is recommended for treatment of localized prostate cancer. Unfortunately, local recurrences occur in up to one-third of patients by 5 years after surgery.1 Furthermore, a combination of hormone therapy with radical prostatectomy in patients with localized disease resulted in 5-year disease-free survival of 64%. 2Effective radiation therapy requires the presence of oxygen.3 As a result of rapid mitotic growth and clonal expansion, tumor cells are usually forced away from vessels beyond effective diffusion distance of oxygen and thrive remarkably well within a hypoxic environment. This tumor hypoxia may lead to resistance to radiation and chemotherapy.4 Hypoxia within solid tumors induces hypoxia-inducible factor (HIF)-1a, 5 and its elevation in prostate cancer cells may attribute to enhanced growth rates, survival and increased metastatic potential. 6HIF-1 is a heterodimer composed of an inducible a-subunit that confers the sensitivity to oxygen and a constitutively expressed b-subunit, aryl hydrocarbon receptor nuclear translocator.7 Under normoxic conditions after a post-translational hydroxylation by prolyl hydroxylase (PHD), HIF-1a interacts with tumor suppressor von-Hippel-Lindau protein and is rapidly degraded via ubiquitin-dependent proteasome pathway. 8 Hypoxia induces a rapid increase in HIF-1a protein stability and transcriptional activity, 9 resulting in the activat...

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Section: Discussionsupporting

confidence: 51%

mentioning

confidence: 99%

Methylseleninic acid downregulates hypoxia‐inducible factor‐1α in invasive prostate cancer

Sinha

Null

Wolter

et al. 2011

Intl Journal of Cancer

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“…A reasonable hypothesis is that selenium compounds act as suppressing agents, possibly by inducing apoptosis and inhibiting cell proliferation [20]. Consistent with this hypothesis, we showed that p-XSC induces Fas-L/JNK-dependent apoptosis in oral cancer cells [21].…”

Section: Introductionsupporting

confidence: 57%

Effects of 1,4-phenylenebis(methylene)selenocyanate on mutagenesis and p53 protein expression in the tongue of lacI rats treated with 4-nitroquinoline-N-oxide

Guttenplan

Chen

Khmelnitsky

et al. 2007

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Previously we showed that the organoselenium compound, 1,4-phenylenebis(methylene) selenocyanate (p-XSC)1 inhibits 4-nitroquinoline-N-oxide (4-NQO)-induced tongue tumorigenesis in Fisher rats. Here we investigate possible mechanisms of this inhibition by monitoring mutagenesis and p53 protein levels in lacI and conventional Fisher rats treated with: 1) a carcinogenic dose of 4-NQO for 10 weeks in drinking water, 2) 4-NQO + p-XSC (15 ppm as selenium), and 3) 4-NQO followed by p-XSC. For mutagenesis studies, rats were euthanized at 7, 12 or 23 wks after the start of 4-NQO. For studies on p53 levels, rats were euthanized at 11, 15 and 23 wks. Appropriate controls were also monitored. In the 4-NQO-alone groups, the mutant fraction (MF) in the cII gene in tongue increased at least 50 × background level. The MF (in units of mutants/10 5 plaque forming units) for the 7, 12 and 23 week 4-NQO groups were respectively, 184 ± 88, 237 ± 105, 329 ± 110. Thus, mutagenesis increased with length of exposure and post-treatment time. p-XSC modestly (ca. 15 -30%) inhibited mutagenesis under all conditions. The inhibition reached significance at the last time point. When p-XSC was administered after 4-NQO, the MF was also modestly reduced. In 4-NQOalone animals, levels of p53 in tongue (determined by Western blotting) were 1, 1.5 and 2.4 control levels at 10, 15 and 23 weeks respectively. In the p-XSC + 4-NQO group, the enhancement in p53 levels by 4-NQO treatment was decreased about 90% at 15 weeks and 45% (P < 0.05) at 23 weeks, and by slightly smaller percentages in corresponding post-treatment groups. p-XSC alone did not alter p53 levels. As p53 levels generally increase in response to DNA damage, these results suggest that p-XSC reduces 4-NQO-induced DNA damage, resulting in reduced 4-NQO-induced mutagenesis and carcinogenesis. However, the fact that p-XSC is also effective when administered after 4-NQO, suggests additional mechanisms of inhibition exist.

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“…Further understanding of the chemotherapeutic mechanisms of candidate compounds may provide a rational approach to using such agents to enhance apoptosis as a strategy for effective chemoprevention of cancer (20). Accumulating evidence supports the hypothesis that apoptosis is a critical mechanism in cancer chemoprevention by Se-containing compounds (21). The synthetic Se-enriched chemotherapeutic polysaccharide κ-selenocarrageenan might inhibit proliferation of K562/ADM cells and induce apoptosis via a Fascaspase-3 pathway (22).…”

Section: Discussionmentioning

confidence: 91%

A novel polysaccharide from Se-enriched Ganoderma lucidum induces apoptosis of human breast cancer cells

Shang¹

2010

Oncol Rep

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Abstract. The novel polysaccharide SeGLP-2B-1 isolated from Se-enriched Ganoderma lucidum, showed antiproliferative activity towards several cancer cell lines in vitro. To investigate the antitumor mechanisms, the apoptotic effects of SeGLP-2B-1 in human breast cancer cells were studied, and the mechanism of this action was further elucidated. Cell apoptosis was detected by Annexin V/PI staining. Caspase activity was assayed using a caspase apoptosis detection kit. Western blot analysis was used to evaluate the levels of procaspase-3, -8, -9, PARP and cytochrome c expression. The results showed that SeGLP-2B-1 inhibited the growth of MCF-7 cells in a time-and dose-dependent manner. Typical characteristics of apoptosis were observed, including morphological changes, sub-G1 cells and DNA ladder formation. Further analysis showed that SeGLP-2B-1 treatment disrupted the mitochondrial membrane potential followed by an increase in the cytochrome c cytosolic levels. Sequentially, SeGLP-2B-1 increased the activities of caspase-9, -3 and poly (ADPribose) polymerase in a time-dependent manner, however, no obvious activation of caspase-8 was observed. Caspase-9 and caspase-3 inhibitor prevented SeGLP-2B-1-induced apoptosis, and the activities of caspases-3, -9 were significantly upregulated by SeGLP-2B-1. Our studies suggest that SeGLP-2B-1 induces apoptosis via a mitochondria-mediated pathway. IntroductionEpidemiological studies suggest that dietary and chemoprevention can provide an important and potentially feasible pathway for reducing cancer occurrence. Selenium (Se) is an essential trace element for a number of metabolically important enzymes (1). Accumulating evidence indicates that a significant inverse relationship between intake of Se and cancer incidence and Se has received considerable attention for its potential role as a chemopreventive agent (2,3). Selenite induce cell necrosis accompanied by damage to cellular DNA and loss of cell-membrane integrity (4,5). Organic selenocompounds induced apoptosis (programmed cell death) without producing changes in membrane integrity or cellular DNA as measured by single-strand breaks in DNA (6-8). Both organic and inorganic compounds of Se have been demonstrated to manifest cancer preventive potential, but several organic seleno-compounds have shown higher anticancer activities, lower toxicity and fewer side effects than selenite, therefore, it is crucial to develop suitable organic Se sources for cancer chemoprevention.Se-containing polysaccharide, a nutritionally available organic seleno-compound, has been shown to promote cancer cell differentiation, suppress cell division and induce programmed cell death by regulating cancer gene expression (9,10). Although several mechanisms have been proposed to account for anticancer effects of Se-containing polysaccharide, selective induction of tumor cell apoptosis may be of particular significance as chemopreventive agents (11)(12)(13)(14).SeGLP-2B-1, a Se-containing polysaccharide, was purified and characterized from the Se-enr...

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Apoptosis is a Critical Cellular Event in Cancer Chemoprevention and Chemotherapy by Selenium Compounds

Cited by 254 publications

References 130 publications

Methylseleninic acid downregulates hypoxia‐inducible factor‐1α in invasive prostate cancer

Methylseleninic acid downregulates hypoxia‐inducible factor‐1α in invasive prostate cancer

Effects of 1,4-phenylenebis(methylene)selenocyanate on mutagenesis and p53 protein expression in the tongue of lacI rats treated with 4-nitroquinoline-N-oxide

A novel polysaccharide from Se-enriched Ganoderma lucidum induces apoptosis of human breast cancer cells

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