PMID: 

J Cancer. 2019 ;10(23):5843-5851. Epub 2019 Oct 6. PMID: 31737120

Abstract Title: 

Cucurbitacin E inhibits cellular proliferation and enhances the chemo-response in gastric cancer by suppressing AKt activation.

Abstract: 

The incidence and mortality rate of gastric cancer has markedly declined over the past few decades, due to the progress and advances in the development of diagnostic and treatment regimens. However, there is still a large portion of patients who are first diagnosed during the advanced stage of gastric cancer when chemotherapy is needed. Unfortunately, resistance to chemotherapeutic agents is the most frequent occurrence during treatment, which indicates a need for the discovery of novel therapeutic anticancer drugs.The tumor-suppression effect of eight different cucurbitacins was evaluated in gastric cancer cell lines, and the Cucurbitacin E (CuE) showing the greatest effect was used in further studies to explore the mechanism and potential synergistic effect of Dox bothand.Compared with other cucurbitacins, CuE showed the greatest antiproliferative activity against the gastric cancer cell lines. Further investigations revealed that CuE suppressed the growth of gastric cancer cell lines through the induction of G2/M arrest and subsequent apoptosis by impairing AKt activation and reducing its expression in gastric cancer cells. Furthermore, our results indicate that CuE can significantly enhance the cytotoxicity of doxorubicin (Dox) bothand.In summary, we present the first evidence of the efficacy of CuE for the inhibition of gastric cancer growth and the synergistic antitumorigenic effect of CuE and Dox, bothand.

read more

PMID: 

Molecules. 2020 Jan 28 ;25(3). Epub 2020 Jan 28. PMID: 32012950

Abstract Title: 

Cucurbitacin E Inhibits Huh7 Hepatoma Carcinoma Cell Proliferation and Metastasis via Suppressing MAPKs and JAK/STAT3 Pathways.

Abstract: 

Cucurbitacin E (CuE), a highly oxygenated tetracyclic triterpene from Cucurbitaceae, has shown to exhibit potent cytotoxic and anti-proliferative properties against several human cancer cells. However, the underlying effects and mechanisms of CuE regarding hepatocellular carcinoma (HCC) have not been well understood. In the current study, unbiased RNA-sequencing (RNA-seq) and bioinformatics analysis was applied to elucidate the underlying molecular mechanism. CuE could significantly inhibit cell proliferation and migration of Huh7 cells, meanwhile CuE exhibited potent anti-angiogenic activity. RNA-seq analysis revealed that CuE negatively regulated 241 differentially expressed genes (DEGs) involved in multiple processes including cytoskeleton formation, angiogenesis and focal adhesion. Further analysis revealed that CuE effectually regulated diversified pharmacological signaling pathways such as MAPKs and JAK-STAT3. Our findings demonstrated the role of CuE in inhibiting proliferation and migration, providing an insight into the regulation of multiple signaling pathways as a new paradigm for anti-cancer treatment strategy.

read more

PMID: 

Cells. 2019 Dec 31 ;9(1). Epub 2019 Dec 31. PMID: 31906106

Abstract Title: 

Novel Mechanistic Insight into the Anticancer Activity of Cucurbitacin D against Pancreatic Cancer (Cuc D Attenuates Pancreatic Cancer).

Abstract: 

Pancreatic cancer (PanCa) is one of the leading causes of death from cancer in the United States. The current standard treatment for pancreatic cancer is gemcitabine, but its success is poor due to the emergence of drug resistance. Natural products have been widely investigated as potential candidates in cancer therapies, and cucurbitacin D (Cuc D) has shown excellent anticancer properties in various models. However, there is no report on the therapeutic effect of Cuc D in PanCa. In the present study, we investigated the effects of the Cuc D on PanCa cells in vitro and in vivoCuc D inhibited the viability of PanCa cells in a dose and time dependent manner, as evident by MTS assays. Furthermore, Cuc D treatment suppressed the colony formation, arrest cell cycle, and decreased the invasion and migration of PanCa cells. Notably, our findings suggest that mucin 13 (MUC13) is down-regulated upon Cuc D treatment, as demonstrated by Western blot and qPCR analyses. Furthermore, we report that the treatment with Cuc D restores miR-145 expression in PanCa cells/tissues. Cuc D treatment suppresses the proliferation of gemcitabine resistant PanCa cells and inhibits RRM1/2 expression. Treatment with Cuc D effectively inhibited the growth of xenograft tumors. Taken together, Cuc D could be utilized as a novel therapeutic agents for the treatment/sensitization of PanCa.

read more

PMID: 

Int J Mol Sci. 2019 Oct 9 ;20(20). Epub 2019 Oct 9. PMID: 31600949

Abstract Title: 

Role of Phytochemicals in Cancer Prevention.

Abstract: 

The use of synthetic, natural, or biological agents to minimize the occurrence of cancer in healthy individuals is defined as cancer chemoprevention. Chemopreventive agents inhibit the development of cancer either by impeding DNA damage, which leads to malignancy or by reversing or blocking the division of premalignant cells with DNA damage. The benefit of this approach has been demonstrated in clinical trials of breast, prostate, and colon cancer. The continuous increase in cancer cases, failure of conventional chemotherapies to control cancer, and excessive toxicity of chemotherapies clearly demand an alternative approach. The first trial to show benefit of chemoprevention was undertaken in breast cancer patients with the use of tamoxifen, which demonstrated a significant decrease in invasive breast cancer. The success of using chemopreventive agents for protecting the high risk populations from cancer indicates that the strategy is rational and promising. Dietary components such as capsaicin, cucurbitacin B, isoflavones, catechins, lycopenes, benzyl isothiocyanate, phenethyl isothiocyanate, and piperlongumine have demonstrated inhibitory effects on cancer cells indicating that they may serve as chemopreventive agents. In this review, we have addressed the mechanism of chemopreventive and anticancer effects of several natural agents.

read more

PMID: 

Nutrition. 2020 Feb ;70:110585. Epub 2019 Sep 13. PMID: 31698296

Abstract Title: 

Zinc and selenium indicators and their relation to immunologic and metabolic parameters in male patients with human immunodeficiency virus.

Abstract: 

OBJECTIVES: Micronutrient deficiencies are common among people living with HIV (PLWHIV). The clinical and immunologic consequences of micronutrient deficiencies have been poorly explored in the context of human immunodeficiency virus (HIV) infection. The aim of this study was to determine the prevalence of zinc and selenium deficiency (dietary intake and serum concentrations) and analyze their associations with absolute CD4+ T-cell counts, inflammation markers, and metabolic disorders in a cohort of antiretroviral-experienced HIV-infected individuals.METHODS: The zinc and selenium intakes of 124 HIV-infected men were estimated using 3-d food records. In a subcohort of 45 individuals, serum zinc and selenium concentrations and proinflammatory cytokines were determined. Body composition, bone mineral density (BMD), CD4+ T-cell counts, lipid profile, glucose, and blood pressure were determined and were associated with zinc and selenium dietary intake and serum concentrations.RESULTS: Of the PLWHIV studied, 58% had suboptimal intake of zinc and 8% demonstrated suboptimal intake of selenium. Serum deficiencies for zinc and selenium were 23.9% and 65.9%, respectively. Zinc and selenium intake were correlated with increased muscle mass. Selenium intake was associated with increased BMD of the lumbar region. An inverse correlation between serum selenium concentration and several proinflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-α) was found.CONCLUSION: Suboptimal zinc and selenium intake and serum concentration deficiencies are highly prevalent in treated HIV-positive individuals and are associated with body composition, BMD, and inflammation. Clinical trials should be designed to explore the effect of zinc and selenium supplementation on metabolic, inflammatory, and immunologic parameters on the HIV-positive population.

read more

PMID: 

Hormones (Athens). 2020 Mar ;19(1):55-59. Epub 2019 Nov 7. PMID: 31701489

Abstract Title: 

Evidence for a manifold role of selenium in infertility.

Abstract: 

This review aimed to assess the evidence from observational and interventional studies in humans and animals regarding the role of selenium (Se) in male and female infertility. As oxidative stress can seriously impair male, and possibly also female, reproductive functions, it can be speculated that the antioxidant properties of Se could constitute one of the pathways by which this element is involved in fertility. Specifically, there are strong indications that Se influences the growth, maturation, and replication of oocytes, though the precise mechanisms have not as yet been fully elucidated. Given that it is not clear at present which tissue sample (blood, serum, seminal plasma, sperm, or follicular fluid) renders the most accurate picture of Se concentration in terms of its role in reproduction, the data are still insufficient to recommend routine assessment of Se status in men and women seeking fertility. Nevertheless, the existing evidence, despite being of limited quantity and somewhat low quality, suggests that Se supplementation (

read more

PMID: 

Hormones (Athens). 2019 Dec ;18(4):451-462. Epub 2019 Dec 10. PMID: 31820398

Abstract Title: 

Effect of selenium supplementation on antioxidant markers: a systematic review and meta-analysis of randomized controlled trials.

Abstract: 

AIM: The aim of this study is the systematic review and meta-analysis of controlled trial studies to assess the antioxidant effects of selenium (Se) supplementation.METHODS: The systematic review and meta-analysis were performed according to the previously published protocol. The PubMed, Web of Sciences, and Scopus databases were meticulously searched for relevant data, without time or language restriction, up to June 1, 2017. All clinical trials which assessed the effect of Se supplementation on antioxidant markers, including oxidative stress index (OSI), antioxidant potency composite (APC) index, plasma malonaldehyde (MDA), total antioxidant capacity (TAC), antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT)), and total antioxidant plasma (TAP), were included. The effect of Se supplementation on antioxidant markers was assessed using standardized mean difference (SMD) and 95% confidence interval (CI). The random-effect meta-analysis method was used to estimate the pooled SMD.RESULTS: In total, 13 studies which assessed the effect of Se supplementation on antioxidant markers were included. The random-effect meta-analysis method showed that Se supplementation significantly increased GPX (SMD = 0.54; 95% CI = 0.21-0.87) and TAC (SMD = 0.39, 95% CI = 0.13, 0.66) levels and decreased MDA levels (SMD = – 0.54, 95% CI = – 0.78, – 0.30). The effect of Se supplementation on other antioxidant markers was not statistically significant (P>0.05).CONCLUSION: The findings showed that Se supplementation might reduce oxidative stress by increasing TAC and GPX levels and decreasing serum MDA, both of which are crucial factors for reduction of oxidative stress.

read more

PMID: 

Nutrients. 2019 Dec 18 ;12(1). Epub 2019 Dec 18. PMID: 31861307

Abstract Title: 

Selenium Supplementation and Prostate Health in a New Zealand Cohort.

Abstract: 

BACKGROUND: There is variable reporting on the benefits of a 200μg/d selenium supplementation towards reducing prostate cancer impacts. The current analysis is to understand whether stratified groups receive supplementation benefits on prostate health.METHODS: 572 men were supplemented with 200µg/d selenium as selinized yeast for six months, and 481 completed the protocol. Selenium and prostate-specific antigen (PSA) levels were measured in serum at pre- and post-supplementation. Changes in selenium and PSA levels subsequent to supplementation were assessed with and without demographic,lifestyle, genetic and dietary stratifications.RESULTS: The post-supplementation selenium (= 0.002) and the gain in selenium (

read more

PMID: 

Redox Biol. 2020 Jan ;29:101409. Epub 2019 Dec 16. PMID: 31926617

Abstract Title: 

Selenomethionine supplementation reduces lesion burden, improves vessel function and modulates the inflammatory response within the setting of atherosclerosis.

Abstract: 

Atherosclerosis is a chronic inflammatory disease of the vasculature characterised by the infiltration of activated neutrophils and macrophages at sites of damage within the vessel wall, which contributes to lesion formation and plaque progression. Selenomethionine (SeMet) is an organic form of selenium (Se), an essential trace element that functions in the regulation of the immune response by both bolstering the endogenous thioredoxin and glutathione antioxidant defence systems and by directly scavenging damaging oxidant species. This study evaluated the effect of dietary SeMet supplementation within a high fat diet fed apolipoprotein E deficient (ApoE) mouse model of atherosclerosis. Dietary supplementation with SeMet (2 mg/kg) increased the tissue concentration of Se, and the expression and activity of glutathione peroxidase, compared to non-supplemented controls. Supplementation with SeMet significantly reduced atherosclerotic plaque formation in mouse aortae, resulted in a more stable lesion phenotype and improved vessel function. Concurrent with these results, SeMet supplementation decreased lesion accumulation of M1 inflammatory type macrophages, and decreased the extent of extracellular trap release from phorbol myristate acetate (PMA)-stimulated mouse bone marrow-derived cells. Importantly, these latter results were replicated within ex-vivo experiments on cultured neutrophils isolated from acute coronary syndrome patients, indicating the ability of SeMet to alter the acute inflammatory response within a clinically-relevant setting. Together, these data highlight the potential beneficial effectof SeMet supplementation as a therapeutic strategy for atherosclerosis.

read more

PMID: 

Environ Sci Pollut Res Int. 2020 Jan 29. Epub 2020 Jan 29. PMID: 31997246

Abstract Title: 

Selenium mitigates cadmium toxicity by preventing oxidative stress and enhancing photosynthesis and micronutrient availability on radish (Raphanus sativus L.) cv. Cherry Belle.

Abstract: 

We aimed to examine the effects of selenium on the tolerance of radish plants CV. Cherri Belle under cadmium phytotoxicity. The biomass accumulation was drastically decreased under Cd toxicity and the supplementary Se maintained the biomass acquisition under Cd pressure. The chlorophyll index (SPAD), PSII efficiency (Fv/Fm), and PSII quantum yield (ΦPSII) were declined in response to Cd treatment, while Se nutrition improved these variables in a dose-dependent manner. The highest HOand MDA contents were observed in the plants fed with 10 mg L Cd. The Cd stress resulted in a considerable decline in the activities of GPX, CAT, and APX antioxidant enzymes, while Se supplementation increased their activities in the Cd-treated plants. Based on the mineral analyses, no Cd was traced in the control plants, while the Cd concentration in bothroots and leaves of the Cd-stressed radish plants increased with increasing the supplemented Cd levels. Compared with plants solely treated with 10 mg LCd, Se nutrition declined the Cd absorption in roots and in leaves. The concentration of evaluated micronutrients including Fe, Mn, Cu, and Zn tended to decrease in the Cd-imposed plants in comparison with control plants. Se nutrition of both stressed and non-stressed radish plants increased the concentrations of the studied microelements, except for Zn in which the individual use of Se led to a decrease in the Zn content. Significant positive and negative correlation values were found among the studied traits and the principle component analysis (PCA) biplot and Ward dendrogram confirmed the results of the correlation analysis. Se proved to be efficient in the alleviation of Cd-triggered deleterious effects by improving biomass acquisition, enhancing chlorophyll biosynthesis and fluorescence, and increasing micronutrient uptake in a dose-dependent manner. Furthermore, the Se alleviation mechanism under Cd stress was also connected with the activation of enzymatic antioxidative protection system as well as with decreasing Cd uptake, transport, and distribution in radish leaves. Altogether, our research strongly suggests the implementation of Se in the growth medium to enhance the tolerance of radish plants under Cd stress.

read more