Therapeutic Uses of Molybdenum
Molybdenum is an essential trace element and is a component of vitamin and mineral supplements. Some therapeutic uses of molybdenum compounds are described in this section.
Lung and breast cancer cells
223 Sustainable one-step synthesis of hierarchical microspheres of PEGylated MoS2 nanosheets and MoO3 nanorods: Their cytotoxicity towards lung and breast cancer cells
Nanotechnology provides an emerging potent alternate mode of cancer therapy. Nanomaterials dispersion or solubility is of particular concern in utilising their full potential applications in biomedical fields. PEGylation of nanomaterials is considered to provide products with stealth properties, and physiological environment with no obvious adverse effects.
The purpose of this work was to develop a sustainable one-step method for fabrication of hierarchical microspheres of PEGylated MoS2 nanosheets using a stoichiometric ratio of Mo(VI) and thiourea.
This study further investigated the cytotoxicity of the PEGylated MoS2 nanosheets towards lung (A549) and breast cancer (MCF-7) cell lines by analysing morphological changes and performing dose-dependent cell proliferation, and cytotoxicity analysis using adenosine 5'-triphosphate (ATP), and lactate dehydrogenase (LDH) assay.
For comparison, MoO3 nanorods were synthesised by simple chemical route and their cytotoxicity towards lung (A549) and breast cancer (MCF-7) cell lines were checked.
The findings suggested that PEGylated MoS2 nanosheets have excellent cytotoxicity towards breast cancer (MCF-7) cell lines, and MoO3 have better cytotoxicity towards lung (A549) cancer cell lines.
This work envisages an accessible foundation for engineering sophisticated biomolecule-MoS2 nanosheets conjugation due to the defect-rich biocompatible surface, to achieve great versatility, additional functions, and further advances in the biomedical field. (C) 2016 Elsevier B.V. All rights reserved.
Kumar, N., George, B. P. A., Abrahamse, H., Parashar, V., and Ngila, J. C.,Sustainable one-step synthesis of hierarchical microspheres of PEGylated MoS2 nanosheets and MoO3 nanorods: Their cytotoxicity towards lung and breast cancer cells, Applied Surface Science, 2017, 396, 8-18.
[PEGylated MoS2: lipoic acid-terminated polyethylene glycol (LA-PEG) grafted onto the surface of MoS2 nanoflakes endowing the nanoflakes with high colloidal stability and very low cytotoxicity.
See Wei Feng, Liang Chen, Ming Qin, Xiaojun Zhou, Qianqian Zhang, Yingke Miao, Kexin Qiu, Yanzhong Zhang and Chuanglong He. Flower-like PEGylated MoS2 nanoflakes for near-infrared photothermal cancer therapy. Scientific Reports 5, Article number: 17422 (2015). doi:10.1038/srep17422.]
MoS2 cancer therapy
Investigation of Thermally Induced Cellular Ablation and Heat Response Triggered by Planar MoS2-based Nanocomposite
In comparison to conventional tumor treatment methods, photothermal therapy (PTT) is one of the innovative therapeutic strategies that employs light to produce the localized heat for targeted ablation of cancer cells.
Among various kinds of heat generation nanomaterials, transition metal dichalcogenide nanosheets, especially-molybdenum disulfide (MoS2) have recently been investigated as one of the promising PTT candidates because of their strong absorbance in the near-infrared (NIR) tissue transparency window and excellent photothermal conversion capability.
In line with the great potential of MoS2-based nanomaterials in biomedical applications, their intrinsic therapeutic performance and corresponding cellular response are required to be continually investigated.
In order to further improve MoS2-based PTT efficacy and dissect the molecular mechanism during heat stimuli, in this study, we successfully designed a novel and effective PTT platform by integration of MoS2 nanosheets with peptide-based inhibition molecules to block the function of heat shock proteins (Hsp90), one type of chaperon proteins that play the protective roles in living system against cellular photothermal response.
Such combined nanosystem could effectively induce cell ablation and viability assays indicated approximately five folds higher PTT treatment efficacy (8.8 % viability) than that of MoS2 itself (48 % viability) upon 808 nm light irradiation.
Moreover, different from the case based on MoS2 alone that could cause tumor ablation through the process of necrosis, the detailed mechanism analysis revealed the inhibition of Hsp90 could significantly increase the photothermal-mediated apoptosis, hence resulting in remarkable enhancement of photothermal treatment.
Such promising studies provide the great opportunity to better understand the cellular basis of light triggered thermal response. Moreover, they can also facilitate the rational design of new generations of PTT platforms toward future theranostics.
Ariyasu, S., Mu, J., Zhang, X., Huang, Y., Yeow, E. K., Zhang, H., and Xing, B.,Investigation of Thermally Induced Cellular Ablation and Heat Response Triggered by Planar MoS2-based Nanocomposite, Bioconjugate chemistry, 2017.
Exposure to sodium molybdate results in mild oxidative stress in Drosophila melanogaster
OBJECTIVES: The study was conducted to assess the redox status of Drosophila flies upon oral intake of insulin-mimetic salt, sodium molybdate (Na2MoO4).
METHODS: Oxidative stress parameters and activities of antioxidant and associated enzymes were analyzed in two-day-old D. melanogaster insects after exposure of larvae and newly eclosed adults to three molybdate levels (0.025, 0.5, or 10 mM) in the food.
RESULTS: Molybdate increased content of low molecular mass thiols and activities of catalase, superoxide dismutase, glutathione-S-transferase, and glucose-6-phosphate dehydrogenase in males. The activities of these enzymes were not affected in females. Males exposed to molybdate demonstrated lower carbonyl protein levels than the control cohort, whereas females at the same conditions had higher carbonyl protein content and catalase activity than ones in the control cohort. The exposure to 10 mM sodium molybdate decreased the content of protein thiols in adult flies of both sexes. Sodium molybdate did not affect the activities of NADP-dependent malate dehydrogenase and thioredoxin reductase in males or NADP-dependent isocitrate dehydrogenase in either sex at any concentration.
DISCUSSION: Enhanced antioxidant capacity in upon Drosophila flies low molybdate levels in the food suggests that molybdate can be potentially useful for the treatment of certain pathologies associated with oxidative stress.
Perkhulyn, N. V., Rovenko, B. M., Lushchak, O. V., Storey, J. M., Storey, K. B., and Lushchak, V. I.,Exposure to sodium molybdate results in mild oxidative stress in Drosophila melanogaster, Redox report : communications in free radical research, 2017, 1-10.
[Drosophila melanogaster = fruit fly. See https://en.wikipedia.org/wiki/Drosophila_melanogaster and Similarity to humans:
“A March 2000 study by National Human Genome Research Institute comparing the fruit fly and human genome estimated that about 60% of genes are conserved between the two species. About 75% of known human disease genes have a recognizable match in the genome of fruit flies, and 50% of fly protein sequences have mammalian homologs. An online database called Homophila is available to search for human disease gene homologues in flies and vice versa. Drosophila is being used as a genetic model for several human diseases including the neurodegenerative disorders Parkinson's, Huntington's, spinocerebellar ataxia and Alzheimer's disease. The fly is also being used to study mechanisms underlying aging and oxidative stress, immunity, diabetes, and cancer, as well as drug abuse.”
Antioxidant and associated enzymes. See http://www.news-medical.net/health/Antioxidant-Enzyme-Systems.aspx Enzymes that catalyze reactions to neutralize free radicals and reactive oxygen species: superoxide dismutase, glutathione peroxidise, glutathione reductase, catalases, lipoic acid. They require co-factors such as selenium, iron, copper, zinc, and manganese for optimum catalytic activity.
“These form the body’s endogenous defence mechanisms to help protect against free radical-induced cell damage. The antioxidant enzymes – glutathione peroxidase, catalase, and superoxide dismutase (SOD) – metabolize oxidative toxic intermediates.]