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 CANCER

Synthesis, characterization and anti-cancer applications of ytterbium doped gadolinium molybdate nanophosphor compound

Nanophosphor compounds with both diagnostic and therapeutic functions are potential for cancer diagnosis and treatment. Lanthanide complexes play a crucial role in cancer diagnosis and therapy. Gadolinium-complexes are commonly used as magnetic resonance imaging (MRI) contrast agents for cancer imaging. The role of a lanthanide, Ytterbium (Yb) in cancer treatment is not unknown. The present work focuses on finding the role of Yb when doped into Gadolinium complexes in cancer treatment. Our results demonstrate that Yb doped Gadolinium molybdate coated with biocompatible silica, effectively inhibited the viability of breast cancer cells after 24 and 48 h of treatment in in vitro, and in contrast the nanophosphor compounds did not affect the viability of healthy cells. Yb doped Gadolinium molybdate also up-regulated apoptotic genes in breast cancer cells. Hence we propose that Yb doped Gadolinium molybdate is a promising theranostic compound. To the best of our knowledge, this is the first report showing anti- cancer nature of Ytterbium-doped into Gadolinium nanophosphors.

J. R. M. Kamaraju, R. R. Kanchi, R. K. Borra, P. S. Reniguntla, and S. Rentala,Synthesis, characterization and anti-cancer applications of ytterbium doped gadolinium molybdate nanophosphor compound, Materials Express, 2019, 9, 882-894.

[Theranostics is a term derived from a combination of the words therapeutics and diagnostics. In this emerging field of medicine, drugs and/or techniques are uniquely combined to simultaneously or sequentially diagnose and treat medical conditions. https://www.news-medical.net/health/What-is-Theranostics.aspx]

Glutathione Depletion in a Benign Manner by MoS2 -Based Nanoflowers for Enhanced Hypoxia-Irrelevant Free-Radical-Based Cancer Therapy

Tumor hypoxia significantly diminishes the efficacy of reactive oxygen species (ROS)-based therapy, mainly because the generation of ROS is highly oxygen dependent. Recently reported hypoxia-irrelevant radical initiators (AIBIs) exhibit promising potential for cancer therapy under different oxygen tensions. However, overexpressed glutathione (GSH) in cancer cells would potently scavenge the free radicals produced from AIBI before their arrival to the specific site and dramatically limit the therapeutic efficacy. A synergistic antitumor platform (MoS2 @AIBI-PCM nanoflowers) is constructed by incorporating polyethylene-glycol-functionalized molybdenum disulfide (PEG-MoS2 ) nanoflowers with azo initiator and phase-change material (PCM). Under near-infrared laser (NIR) irradiation, the photothermal feature of PEG-MoS2 induces the decomposition of AIBI to produce free radicals. Furthermore, PEG-MoS2 can facilitate GSH oxidation without releasing toxic metal ions, greatly promoting tumor apoptosis and avoiding the introduction of toxic metal ions. This is the first example of the use of intelligent MoS2 -based nanoflowers as a benign GSH scavenger for enhanced cancer treatment.

S. Wu, X. Liu, J. Ren, and X. Qu,Glutathione Depletion in a Benign Manner by MoS2 -Based Nanoflowers for Enhanced Hypoxia-Irrelevant Free-Radical-Based Cancer Therapy, Small, 2019, e1904870. https://doi.org/10.1002/smll.201904870

               

CANCER

Layered MoS2 nanosheets modified by biomimetic phospholipids: Enhanced stability and its synergistic treatment of cancer with chemo-photothermal therapy

Cancer is a huge challenge humanity facing today, and single chemical treatments inevitably have shortcomings such as poor selectivity and large side effects. This paper constructed an egg yolk phospholipids modified molybdenum disulfide (MoS2) nanocarrier system for the treatment of tumors via the combination of chemotherapy and photothermal therapy. The lipid-modified layered MoS2 (MoS2-Lipid) nanocomposite was synthesized by simple physical adsorption. The lipid modification strongly enhanced the stability of MoS2 nanosheets and the nanocarrier has a large drug loading amount with pH dependent DOX release profile, an excellent photothermal property, and an ideal cellular uptake property. Therefore, we combined chemotherapy and photothermal therapy to treat tumors synergistically. Through in vitro cell experiments, pure nanocomposite had no obvious cytotoxicity to cells, and the synergistic treatment of tumors by chemotherapy and photothermal therapy was more effective than any single treatment. More importantly, in vivo experiments indicated that lipid modification enhanced the accumulation of the nanocarrier in mice tumors, thus a better photothermal performance could be seen compared with original MoS2 nanosheets. In summary, the MoS2-lipid nanocomposite is a promising nanocarrier for the treatment of tumors by chemo and photothermal therapy.

M. Xie, N. Yang, J. Cheng, M. Yang, T. Deng, Y. Li, and C. Feng,Layered MoS2 nanosheets modified by biomimetic phospholipids: Enhanced stability and its synergistic treatment of cancer with chemo-photothermal therapy, Colloids and surfaces. B, Biointerfaces, 2019, 110631. https://doi.org/10.1016/j.colsurfb.2019.110631

Biological effects of molybdenum compounds in nanosized forms under in vitro and in vivo conditions [cancer]

Nanoparticles of transition metal dichalcogenides, particularly of molybdenum (Mo), have gained a lot of focus due to their exceptional physicochemical properties and the growing number of technological applications. These nanoparticles are also considered as potential therapeutic tools, biosensors or drug carriers. It is crucial to thoroughly examine their biocompatibility and ensure safe usage. The aim of this review is to analyze the available data on the biological effects of different nanoforms of elemental Mo and its compounds. In the reviewed publications, different conditions were described, including different experimental models, examined nanoforms, and their used concentrations. Due to these differences, the results are rather difficult to compare. Various studies classify Mo related nanomaterials as very toxic, mildly toxic or non-toxic. Similarly, the mechanisms of toxicity proposed in some studies are different, including oxidative stress induction, physical membrane disruption or DNA damage. Quite promising, however, are the potential medical applications of MoS2 nanoparticles in therapy of cancer and Alzheimer's disease. Further studies on biocompatibility of nanomaterials based on Mo compounds are warranted.
Z. Sobanska, L. Zapor, M. Szparaga, and M. Stepnik,Biological effects of molybdenum compounds in nanosized forms under in vitro and in vivo conditions, International journal of occupational medicine and environmental health, 2019.
DOI: https://doi.org/10.13075/ijomeh.1896.01411

               

PROSTATE CANCER

Antiproliferative effect of MoS2 in human prostate cancer cell lines

In this investigation, the anti-proliferative activity of a novel molybdenum complex was distinguished on LNCaP (as an androgen-dependent), PC3 (as an androgen-independent) cancer cells, and normal PBD2-fib cells (as a control) using MTT assay, flow cytometry, RT-qPCR, and western blotting. The MoS2 was prepared by the hydrothermal method, and the synthetic MoS2 characterized using XRD, EDX, FESEM, HRTEM, and Raman spectroscopies to confirm the success of the synthesis and the unique crystal structure. The cells were treated with different concentrations of MoS2 (0, 5, 10, 20, 35 and 50 mu g ml+/-) for 24, 48 and 72 h. The obtained results showed that the IC50 values for LNCaP (21.02+/-0.09 mu g ml+/-) and PC3 (23.03+/-0.07 mu g ml+/-) were significantly lower than that recorded for normal fibroblast cells (41.56+/-0.012 mu g ml-1). Flow cytometry findings demonstrated that the complex is effective in reducing cancer cell viability via apoptosis. RT-qPCR data showed a decrease in BCL2 expression and increases in BAX and P53 gene expression, which were also correlated with the synthetic complex response. The expression of P53 protein increased in LNCaP and PC3 cells after treating with MoS2. Also, these data show the anti-tumor properties of synthetic molybdenum complexes in prostate cancer cells. To conclude, the results indicated that the novel design of nanoparticles can be created a new generation of nano-therapeutics strategies in different types of cancer.

N. Askari, and M. B. Askari, Antiproliferative effect of MoS2 in human prostate cancer cell lines, Biomedical Physics & Engineering Express, 2019, 5, 065024.

CANCER

Pluronic F127-functionalized molybdenum   oxide nanosheets with pH-dependent degradability for chemo-photothermal cancer therapy

Traditional cancer therapies carry a risk of serious side effects and toxicity. Developing an alternative treatment modality that is highly effective, has low toxicity and is noninvasive is urgently required. Here, we exploited molybdenum   oxide (MoOx) nanosheets as a drug carrier and degradable photothermal agent to provide a chemo-photothermal combination cancer therapy. The MoOx nanosheets were synthesized by a one-pot hydrothermal method and then modified with pluronic F127 to improve physiological stability and biocompatibility. The F127-modified nanosheets (MoOX@F127) showed ultrahigh drug loading efficiency (DLE) of doxorubicin (DOX) (DLE%; 65%, W(load DOX)/[W(load DOX)+WMoOx@F127]), strong near-infrared (NIR) absorption and desirable pH-dependent degradability. After intravenous injection, MoOx@F127 nanosheets were degraded at physiological pH and were rapidly excreted from normal organs, while they were effectively accumulated and retained long-term in the more acidic tumor tissue. This simultaneously ensured effective tumor ablation after NIR irradiation and avoided long-term retention and toxicity in vivo. Compared to chemotherapy or photothermal therapy alone, in vitro and in vivo tumor ablation studies have shown a notably improved synergistic effect of the combination therapy. Our study presents a multifunctional nanosystem with a desirable degradability for chemo-photothermal combination cancer therapy that has great potential in biomedical applications.

Y. Chen, A. R. Khan, D. Yu, Y. Zhai, J. Ji, Y. Shi, and G. Zhai,Pluronic F127-functionalized molybdenum   oxide nanosheets with pH-dependent degradability for chemo-photothermal cancer therapy, Journal of colloid and interface science, 2019, 553, 567-580.

               

 

               

 

Molybdenum and cancer

Molybdenum trioxide has been reported to be weakly carcinogenic in mice in a short-term (30 week) lung adenoma assay at high doses (4 750 mg/kg total) but not at lower doses [Stoner et al., 1976]. The reported carcinogenicity of molybdenum orange pigment (a mixture of lead chromate and lead molybdate) injected subcutaneously injection to rats is likely due to the lead and chromium rather than the molybdenum since lead chromate is a carcinogen [Maltoni (a), 1976; Maltoni (b), 1976].

Stoner, G. D., Shimkin, M. B., Troxell, M. C., Thompson, T. L. and Terry, L. S., Cancer Res., 1976, 36, 1744.
Maltoni, C., Ann. N.Y. Acad. Sci., 1976, 271, 431.
Maltoni, C., Ann. N.Y. Acad. Sci., 1976, 271, 444.

In the rat azoxymethane induced aberrant crypt foci have been suggested to be biological precursors to colon cancers. The effects of 41 potential chemopreventive agents in the F344 rat using the inhibition of carcinogen-induced aberrant crypt foci in the colon as the measure of efficacy were assessed [Wargovich et al., 1996]. Aberrant crypt foci were induced by the carcinogen azoxymethane. Twenty-three agents did not inhibit aberrant crypt foci; among these were several agents, including sodium molybdate, that promoted the development of aberrant crypt foci at one or both doses tested. The average yield of aberrant crypts for the azoxymethane-only group was 88 8 aberrant crypt foci/colon. When the diet included sodium molybdate (0.05 g/kg diet) the yield of aberrant crypts was 103 8 significantly greater than control group.

Wargovich, M.J., Chen, C.D., Jimenez, A., Steele, V.E., Velasco, M., Stephens, L.C., Price, R., Gray, K., Kelloff, G.J., Aberrant Crypts As A Biomarker For Colon-Cancer - Evaluation Of Potential Chemopreventive Agents In The Rat, Cancer Epidemiology Biomarkers & Prevention, 1996, 5, 355-360.

The potential toxicities of organic and some inorganic compounds have been predicted by a computer program which correlates toxicity with molecular properties [Lewis et al.,1996]. The program is called COMPACT (Computer Optimised Molecular Parametric Analysis for Chemical Toxicity: CYP1A and CYP2E1). Evaluations were also made by Hazard expert, and for metal ion redox potentials; and these, together with COMPACT, were compared with results from the Ames test for mutagenicity in Salmonella, the micronucleus test and 90-day subchronic rodent pathology. According to the abstract, molybdenum trioxide is a metal compound with a redox potential of the metal/metal ion indicative of possible carcinogenicity and the prediction for carcinogenicity was positive for molybdenum trioxide. However, it is clear from the body of the paper that this statement is most misleading. The programs gave no prediction for molybdenum trioxide. The reference to the redox potential is to the Mo(III)/Mo(IV) couple allegedly 0.32 V oxidising and so having carcinogenic potential. This potential is hardly relevant since MoO3 is Mo(VI) and the relevant potential is Mo(VI)/Mo(V), 0.4 V.

Lewis, D.F.V., Ioannides, C., Parke, D.V., Compact And Molecular-Structure In Toxicity Assessment - A Prospective Evaluation Of 30 Chemicals Currently Being Tested For Rodent Carcinogenicity, Environmental Health Perspectives, 1996, 104, 1011-1016.

Cobalt sulfate hydrate, gallium arsenide, molybdenum trioxide, vanadium pentoxide, and nickel sulfate heptahydrate were tested in the Syrian hamster embryo (SHE) assay in order to increase the SHE assay database for heavy metals [Kerckaert et al., 1996]. All five compounds produced significant morphological transformation {MT) at one or more doses in a dose-responsive manner. Cobalt sulfate hydrate, gallium arsenide, molybdenum trioxide, and nickel (II) sulfate heptahydrate were all positive with a 24-h exposure, suggesting direct DNA perturbation. Vanadium pentoxide was negative with a 24-h exposure, but positive with a 7-day exposure. This pattern of response (24-h SHE negative/7-day SHE positive) has been seen with other chemicals which have tumour promotion-like characteristics. MoO3 in a 24 h exposure to SHE cells with culture medium as the solvent gave a significant increase in SHE cell MT in four doses =/> 75 microg/ml and 67% cytotoxicity at the top dose of 200 microg/ml. The Mo value compares with Ni 5 microg/ml and Co 1 microg/l.

Kerckaert, G.A., Leboeuf, R.A., Isfort, R.J., Use Of The Syrian-Hamster Embryo Cell-Transformation Assay For Determining The Carcinogenic Potential Of Heavy-Metal Compounds, Fundamental And Applied Toxicology, 1996, 34, 67-72.

Chronic exposure of animals to molybdenum oxide fumes (53 mg/m3 for 1 h daily) produced pulmonary irritation and fatty changes in the liver and the kidney, but no deaths occurred [Smyth, 1956.]

Smyth, H.E., Hygienic standard for daily inhalation. Ind Hyg Q, 1956,17,129-185.

The results of a study of the respiratory effects of inhalation of air-borne MoO3dust during two years are summarised in Table 7.2 [Chan et al., 1998]. Although the blood concentration of Mo increased as a consequence of the Mo exposure toxic symptoms were not observed. Prolonged inhalation of MoO3 dusts was harmful to the respiratory system of the mice and rats. The effect of MoO3 is similar to that of talc, nickel oxide and nickel subsulfide and irritants generally in inhalation studies. There is, however, a species dependence and some of the effects are marginal. Whether inhalation of MoO3 induces carcinomas is of particular interest. The number of animals experiencing adenoma or carcinoma at the highest MoO3 exposures were: male mice 9/50 and 10/50, female mice 9/49 and 6/49; male rats 3/50 and 1/50, female rats 2/50 and 0/50. The exposure (100 mg m-3) is ten times the US workplace threshold limit value. The authors comment that MoO3 is not mutagenic.

Chan, P.C., Herbert, R.A., Roycroft, J.H., Haseman, J.K., Grumbein, S.L.,Miller, R.A., Chou, B.J., Lung tumor induction by inhalation exposure to molybdenum trioxide in rats and mice, Toxicological Sciences, 1998, 45, 58-65.

Serum Concentrations of 15 Elements Among Helicobacter Pylori-Infected Residents from Lujiang County with High Gastric Cancer Risk in Eastern China

Helicobacter pylori (H. pylori) infection can interfere with the absorption of most elements, and the variations of some element levels are related to the incidence of gastric cancer. However, there have been conflicting results concerning the influence of H. pylori infection on serum element levels. The present study aimed to compare the serum element concentrations of H. pylori-infected local residents with uninfected residents from Lujiang County with high gastric cancer risk in Eastern China. We used data and serum samples from the H. pylori screening-survey program which was a cross-sectional study. We took 155 samples randomly from the screening survey, identified 74 H. pylori-positive residents and 81 H. pylori-negative residents by a serological test. The serum concentrations of 15 elements (calcium, magnesium, iron, zinc, selenium, copper, molybdenum, chromium, cobalt, nickel, lead, cadmium, mercury, arsenic, and aluminum) were determined using inductively coupled plasma mass spectrometry. Serum cobalt was found at higher levels in the H. pylori-infected residents than the H. pylori-uninfected residents (0.246 vs 0.205g/L, P=0.022), but no statistically significant differences in the serum levels of other elements were found. This is the first study to report the serum concentrations of 15 elements and their relationships with the infection status of H. pylori among local residents from Lujiang County with high gastric cancer risk. Although the International Agency for Research on Cancer has classified cobalt and other soluble cobalt salts as possibly carcinogenic to human beings, our results may provide a clue to the relationships between cobalt, H. pylori, and gastric cancer.

A. L. Hu, L. Li, C. L. Hu, D. M. Zhang, C. Wang, Y. Jiang, M. Zhang, C. M. Liang, W. J. Chen, Q. L. Bo, and Q. H. Zhao,Serum Concentrations of 15 Elements Among Helicobacter Pylori-Infected Residents from Lujiang County with High Gastric Cancer Risk in Eastern China, Biological trace element research, 2018, 186, 21-30.

Anti-cancer properties of molybdenum

Sodium molybdate administered in drinking water has a protective action against the induction of cancer in rats by organic N-nitroso compounds [Luo , X.-M.et al.,1983]. Inhibitory effects of molybdenum on oesophageal and forestomach carcinogenesis in rats have been reported [Komada, H. et al., 1990] and the effect of dietary molybdenum on oesophageal carcinogenesis in rats induced by N-methyl-N-benzylnitrosamine [Wei, H.-J et al., 1985]. Effects of molybdenum and tungsten on mammary carcinogenesis are found in SD rats.[ Seaborn and Yang, 1993]. Molybdenum supplementation affects N-nitroso- N-methylurea-induced mammary carcinogenesis and molybdenum excretion in rats [Kopf-Meyer, 1979].

Luo, X. M., Wei, H. J. and Yang, S. P., J.Nat.Cancer Inst.,1983, 71, 75.
Komada, H., Nakagawa, M., Yamamura, M., Hioki, K. and Yamamoto, Cancer Res., 1990, 50, 2418.
Wei, H. J., Luo, X. M. and Yang, S. P., J.Nat.Cancer Inst., 1985, 74, 469.
Seaborn, C. D. and Yang, S. P., Biol. Trace Elem. Res., 1993, 39, 245.
Kopf-Meyer, P., Naturforsch., 1979, 34, 1174.

Molybdenum dichloride has anti-tumour agent properties [Koizumi et al., 1995]. Suppressive effects of molybdenum on hepatotoxicity of N-nitrosodiethylamine in rats have been reported.

Koizumi, T., Tajima, K., Emi, N., Hara, A., Suzuki, K.T., Suppressive Effect Of Molybdenum On Hepatotoxicity Of N-Nitrosodimethylamine In Rats, Biological & Pharmaceutical Bulletin, 1995, 18, 460-462.

The beneficial effect of the molybdenum is due to the denitrosation of the nitroso compound. Molybdenum is also a biological antagonist of cancer-producing copper [Nederbragt, 1982].

Nederbragt, H., Br. J. Nutr., 1982, 48, 353.

Molybdenum prevents the carcinogenesis of N-nitroso compounds [Koizumi et al., 1995]. Male Wistar rats weighing 170-190 g were pretreated with sodium molybdate, Na2MoO4(1.24 mmol/kg body weight, i.p., once a day) for 3 d and on day 4, they were exposed to N-nitrosodimethylamine (50 mg/kg body weight, once, i.p.). Na2MoO4-pretreatment prevented both nitrosodimethylamine-induced DNA damage and disruption of the metabolism of K and Ca but rather enhanced lipid peroxidation.Mo prevented N nitrosodimethylamine-induced DNA damage by preventing disruption of intracellular Ca metabolism while stimulating the metabolism of the nitroso compound via a nontoxic pathway.

Koizumi, T., Tajima, K., Emi, N., Hara, A. and Suzuki, K.T., Biol. Pharm. Bull., 1995, 18, 460.

 Protective effect of sodium molybdate against hepatotoxicity in rat

The hepatoprotective potential of sodium molybdate was investigated against liver damage in rats induced by carbon tetrachloride.

Carbon tetrachloride increased the serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in rats and reduced levels of the antioxidant enzymes superoxide dismutase and catalase in the liver.

Treatment with sodium molybdate attenuated these changes to nearly undetectable levels.

The histopathological changes induced by carbon tetrachloride were also significantly attenuated by sodium molybdate treatment.

Sodium molybdate can protect the liver against carbon tetrachloride-induced oxidative damage in rats. This hepatoprotective effect might be attributable to modulation of detoxification enzymes and/or its antioxidant and free radical scavenger effects.

Eidi, A., Eidi, M., Al Ebrahim, M., Rohani, A. H., and Mortazavi, P., Protective effects of sodium molybdate on carbon tetrachloride-induced hepatotoxicity in rats, Journal of Trace Elements in Medicine and Biology, 2011, 25, 67-71.

Bioaccumulation of Zn, Mn and Mo in healthy and cancerous mammary glands in dogs

The investigation was to find the dependence among Zn, Mn and Mo in healthy (no pathological lesions) mammary glands in bitches and in mammary gland neoplastic tumors of bitches to confirm a hypothesis which that neoplastic tissues accumulate higher amounts of some elements as compared to tissues at the state of homeostasis.

The research material comprised mammary gland tumors obtained from bitches collected during routine surgical procedures and mammary glands obtained during post mortem examination from bitches which comprised the control group.

Due to great morphological variability of the bitch mammary gland tumors, the investigations were performed on certain groups of neoplasms of epithelial origin (carcinomas and adenocarcinomas) which were separated on the basis of histopathological examinations.

In the control group a lower content of particular elements was observed as compared to tissues undergoing the neoplastic process. There were also highly significant differences observed (p <= 0.01) between the investigated groups. For neoplastic tissues more zinc and molybdenum were observed in the group of carcinomas and a lower content in the group of adenocarcinomas. For manganese the dependence was reversed.

Skibniewska, Ewa M.; Kosla, Tadeusz; Skibniewski, MihalBioaccumulation of Zn, Mn and Mo in healthy and cancerous mammary glands in dogsTrace Elements and Electrolytes,2012, 29, 1, 42-47.

Molybdate and cancer

Antiproliferative activity of vanadate, tungstate, and molybdate in the PC-3 human prostate cancer cell line.

The differential antiproliferative effects of vanadate, tungstate, and molybdate on human prostate cancer cell line PC-3 were compared.

The three oxoanions can cause G2-M cell cycle arrest as evidenced by the increase in the level of phosphorylated Cdc2 [cell division control protein 2, a key player in cell cycle regulation] at its inactive Tyr-15 site.

Even if the difference in cellular uptake among the three oxoanions is excluded from the possible factors affecting their antiproliferative activity, vanadate exerted a much more potent effect in PC-3 cells than the other two oxoanions. Reactive oxygen species (ROS)-mediated degradation of Cdc25C rather than Cdc25A or Cdc25B is responsible for vanadate-induced G2-M cell cycle arrest.

A mechanism is proposed to account for the different effects of the three oxoanions in biological systems beyond just considering that they are structural analogs of phosphate. It is suggest that ROS formation is unlikely to be involved in the biological function of tungstate and molybdate, whereas the redox properties of vanadium may be important for its pharmacological effects.

Liu, Tong-Tong; Liu, Yan-Jun; Wang, Qin; Yang, Xiao-Gai; Wang, Kui Reactive-oxygen-species-mediated Cdc25C degradation results in differential antiproliferative activities of vanadate, tungstate, and molybdate in the PC-3 human prostate cancer cell line.Journal of Biological Inorganic Chemistry 2012, 172, 311-20.

[Antiproliferative: inhibiting cell growth, e.g antiproliferative effects on tumor cells;a substance used to prevent or retard the spread of cells, especially malignant cells, into surroundingtissues.]

[Entry into each phase of the cell-cycle is regulated by receptor collectives, cell-cycle checkpoints. One theme emerging in drug discovery is to develop agents that target the cell-cycle checkpoints that are responsible for the control of cell-cycle phase progression. It is clear that the cell-cycle checkpoints can regulate the quality and rate of cell division; These checkpoints allow progression through the cell-cycle or arrest in response to DNA damage to allow time for DNA repair.The G2 checkpoint allows the cell to repair DNA damage before entering mitosis DiPaola,R.S., Clin. Cancer Res., 2002, 8: 3512–3519.]

Molybdenum(VI) glutathione complex binding to DNA

The complex [Mo(VI)(GS)(Cl)(H2O)]Cl2 (= MoG) was synthesized in aqueous solution and characterised analytically and spectroscopically.It is diamagnetic, hence molybdenum(VI), and a 1:2 electrolyte.

The binding of MoG with calf thymus DNA was studied by spectroscopic titration,monitoring the DNA 260 nm band and the S -> Mo LMCT band of the complex at 225 nm. The interaction ratio was 1:0.70 (DNA:MoG) and the binding constant of DNA-MoG was 4.8 x 105 M-1, a value indicative of intercalative binding.

Glutathione

Glutathione

Selim, M., Saha, A., Mukherjea, K. Synthesis, characterization, and DNA binding of the biologically relevant novel cationic molybdenum(VI)-glutathione complex [Mo(GS)(Cl)(H(2)O)]Cl(2), Monatshefte fur Chemie, 2012, 143,2, 227-233.

Oxometallate interactionswith Sarcoplasmic reticulum calcium ATPase

Interest in oxometalate and polyoxometalate applications to medicine and pharmacology is due to their anti-cancer, anti-diabetic properties and treatment of neurodegenerative diseases.

Sarcoplasmic reticulum (SR) vesicles, containing a large amount of Ca2+-ATPase, an enzyme that accumulates calcium by active transport using ATP, are a useful model to study the effects of oxometalates on calcium homeostasis.

Molybdate is an inhibitor of the Ca2+-ATPase enzyme but much less so than are polyoxovanadate and polyoxoniobate which are strong inhibitors. IC50 values [half maximal inhibitory concentrations/microM, measuring the effectiveness of the compounds in inhibiting SR Ca Ca2+ATPase] were:decavanadate, 15; decaniobate, 50; vanadate, 35; tungstate, 400; molybdate, 45000.

The inhibition affects,inter alia, calcium homeostasis, cell signalling and cell bioenergetics. An oxometalate may act as a phosphate analogue, as a transition-state analogue in enzyme-catalysed phosphoryl group transfer processes, or as a potentially nucleotide-dependent enzyme modulator or inhibitor.

The inhibition of specific enzymes by decameric species of V and Nb may contribute to their anti-cancer, anti-viral and anti-diabetic activities.

Overall, these results indicate a need to understand the impact of groups V and VI metals on health and in particular, the effect of these metals on different types of biological tissue, such as membrane proteins as these are one of the first potential cellular targets upon metal exposure. The potential impact on the ion pumps will affect, for instance, the modulation of calcium homeostasis, and thus also the regulation and bioenergetics of muscle contraction/relaxation in muscle cells, as well as others processes in non-muscle cells, such as cytoskeleton dynamics, apoptosis/necrosis, oxidative-stress alterations and mitochondrial activity.

Fraqueza, G., Ohlin, C. A., Casey, W.H., Aureliano, M. Sarcoplasmic reticulum calcium ATPase interactions with decaniobate, decavanadate, vanadate, Journal of Inorganic Biochemistry, 2012, 107, 82-89.

A study of the relationship between trace element Mo and gastric cancer

AIM: To study the relationship between trace element Mo and gastric cancer.

MATERIALS AND METHODS: Soil samples were collected according to its type in different areas of Jiangxi Province; available molybdenum content in soil was measured by catalytic polarography and rank correlation method was used to analyse correlation between the mean of soil available molybdenum and mortality rate of gastric cancer in each county and city in Jiangxi Province. Gastric cancer cases were selected from the authors’ hospital, occiput hair was collected to measure its molybdenum content with an atomic absorption spectrograph and controls were selected from the same hospital for comparison. Gastric cancer cases were selected from three hospitals at the same time, blood samples were taken on an empty stomach and serum molybdenum contents were measured with the atomic absorption spectrograph, and controls were selected from the same hospitals. Blind method was used in the whole course (chemical analysts did not know the source and nature of samples).

RESULTS: A negative correlation existed between soil available molybdenum content and mortality rate of gastric cancer ( r = -0.285, P < 0.05); hair molybdenum contents of gastric cancer cases were lower than those of healthy controls (0.308 μg/g ± 0.673 μg/g and 0.707 μg/g ± 0.561 μg/g respectively, P < 0.01 ); serum molybdenum contents of patients were also lower than those of healthy controls ( 21.84 μg/L ± 7.49 μg/L and 25.38 μg/L ± 8.58 μg/L respectively, P < 0.05).

CONCLUSION: Deficiency of molybdenum may be one of the risk factors in gastric cancer.

G.-H. Cao, S.-M. Yan, Z.-K. Yuan, L. Wu, and Y.-F. Liu,A study of the relationship between trace element Mo and gastric cancer, World journal of gastroenterology, 1998, 4, 55.

 

DISTRIBUTION OF SELENIUM AND MOLYBDENUM AND CANCER MORTALITY IN NIIGATA, JAPAN

Selenium and molybdenum have inhibitory effects on gastrointestinal carcinogenesis. We investigated the levels of selenium and molybdenum in sediments and mortality from cancers at specific sites in 19 areas of Niigata Prefecture, Japan, and compared these factors. The average concentrations of selenium and molybdenum were 0.44 +/- 0.19 ppm (mu g/g dry weight; mean +/- standard deviation) and 3.82 +/- 1.03 ppm, respectively. Selenium was not associated significantly with cancer mortality. There were inverse correlations between molybdenum levels and female mortality from cancers of the esophagus (r = -.446, .05 < p < .1) and rectum (r = -.529, p < .05). Molybdenum was correlated positively with female mortality from cancer of the pancreas (r = .603, p < .01). Further investigations are needed for causal interpretation of these results.

H. Nakadaira, K. Endoh, M. Yamamoto, and K. Katoh,DISTRIBUTION OF SELENIUM AND MOLYBDENUM AND CANCER MORTALITY IN NIIGATA, JAPAN, Archives of Environmental Health, 1995, 50, 374-380.

 

Users of the Database should be aware that inclusion of an abstract in the Database does not imply any IMOA endorsement of the accuracy or reliability of the reported data or the quality of a publication.