Janus-faced molecule

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A Janus molecule (or Janus-faced molecule) is a molecule which can represent both beneficial and toxic effects. The term Janus-faced molecule is derived from the ancient Roman god, Janus. Janus is depicted as having two faces; one facing the past and one facing the future. [1] This is synonymous to a Janus molecule having two distinct purposes: a beneficial and a toxic purpose depending on its quantity.

Contents

Examples

Examples of a Janus-faced molecule are nitric oxide [2] and cholesterol. [3] In the case of cholesterol, the property that makes cholesterol useful in cell membranes, namely its absolute insolubility in water, also makes it lethal. When cholesterol accumulates in the wrong place, for example within the walls of an artery, it cannot be readily mobilized, and its presence eventually leads to the development of an atherosclerotic plaque.

One such example of a Janus-faced molecule is S100A8/A9 protein complex; this complex is associated with autoimmune and abnormal growth of cells disorders. S100 is integral in the fight against cancer, S100 induces phagocytes that phagocytize malignant tumor cells which results in apoptosis. [4]

Proteoglycans are another class of molecules that display this duality, under certain chemical conditions these molecules can emerge as inhibitors or promoters. [5] Recent studies have shown that proteoglycans can play an integral role in the metastasis of cancer. Another molecule that falls within this class of molecules is DKK1. This molecule's presence can trigger cancers to display both metastatic as well as anti-metastatic properties especially pertaining to breast cancers. It has been studied that DKK1 secretion can be associated with promoting breast cancer metastasis to the bone as well as the suppression of metastasis to the lungs. [6] Botulinum neurotoxins also portray these dichotomous roles. This specific molecule is formed by Clostridium Botulinum, a spore forming bacteria. If this bacteria contaminates food, the results can be fatal and can lead to death. Yet, despite their toxicity which is lethal even in small doses, these molecules can be used in a wide array of pharmacological applications; one such application is the one utilized in cosmetology . [7]

Gamma peptide nucleic acid (PNA) (synthetic DNA and RNA analogs) is another Janus molecule which slips between DNA strands. [8] The gamma PNA could be inserted between strands of DNA or RNA to recognize sequences or elements that could potentially cause known diseases through its bifacial recognition. It does so by inserting itself when the DNA or RNA strand is undergoing transcription to conduction transcriptional regulation. However, there are still ongoing challenges with this Janus molecule that requires further research and experimentation. [9]

Some fungi are capable of producing secondary metabolites called mycotoxins which are toxic and affect human and animal health. [10] Mycotoxins are often found in farmed ingredients such as corn and rice while it is being harvested or kept in storage; When these ingredients are largely manufactured towards humans and animals, there is the possibly of consumption of these toxins. The toxicity of these mycotoxins were intensively studied and appeared to be affective in killing microbes as well as inhibiting/killing tumor cell growth. [11] This exihibits janus-faced molecule characteristics because it kills indiscriminitely. A consequence of using mycotoxins against tumor cell growth in cancer treatment is an increase risk of mutations.

See also

Related Research Articles

<span class="mw-page-title-main">Metastasis</span> Spread of a disease inside a body

Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, are metastases (mets). It is generally distinguished from cancer invasion, which is the direct extension and penetration by cancer cells into neighboring tissues.

<span class="mw-page-title-main">Exotoxin</span> Toxin from bacteria that destroys or disrupts cells

An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface.

An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism. Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolates that interfere with the use of folic acid; thus, competitive inhibition can occur, and the presence of antimetabolites can have toxic effects on cells, such as halting cell growth and cell division, so these compounds are used in chemotherapy for cancer.

The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal cells that can differentiate into a variety of cell types. EMT is essential for numerous developmental processes including mesoderm formation and neural tube formation. EMT has also been shown to occur in wound healing, in organ fibrosis and in the initiation of metastasis in cancer progression.

<span class="mw-page-title-main">MMP7</span> Protein-coding gene in humans

Matrilysin also known as matrix metalloproteinase-7 (MMP-7), pump-1 protease (PUMP-1), or uterine metalloproteinase is an enzyme in humans that is encoded by the MMP7 gene. The enzyme has also been known as matrin, putative metalloproteinase-1, matrix metalloproteinase pump 1, PUMP-1 proteinase, PUMP, metalloproteinase pump-1, putative metalloproteinase, MMP). Human MMP-7 has a molecular weight around 30 kDa.

<span class="mw-page-title-main">BCL3</span> Protein-coding gene in the species Homo sapiens

B-cell lymphoma 3-encoded protein is a protein that in humans is encoded by the BCL3 gene.

<span class="mw-page-title-main">Heparanase</span> Mammalian protein found in Homo sapiens

Heparanase, also known as HPSE, is an enzyme that acts both at the cell-surface and within the extracellular matrix to degrade polymeric heparan sulfate molecules into shorter chain length oligosaccharides.

The perinucleolar compartment (PNC) is a subnuclear body characterized by its location at the periphery of the nucleolus. The PNC participates in the patterned compartmentalization inside the nucleus to organize the specialized functions. It is almost exclusively found in oncogenic cells and enriched with RNA binding proteins as well as RNA polymerase III transcripts.

<span class="mw-page-title-main">RhoC</span> Protein-coding gene in the species Homo sapiens

RhoC is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOC.

<span class="mw-page-title-main">S100A11</span> Protein-coding gene in the species Homo sapiens

S100 calcium-binding protein A11 (S100A11) is a protein that in humans is encoded by the S100A11 gene.

A metastasis suppressor is a protein that acts to slow or prevent metastases from spreading in the body of an organism with cancer. Metastasis is one of the most lethal cancer processes. This process is responsible for about ninety percent of human cancer deaths. Proteins that act to slow or prevent metastases are different from those that act to suppress tumor growth. Genes for about a dozen such proteins are known in humans and other animals.

<span class="mw-page-title-main">MTA3</span> Protein-coding gene in the species Homo sapiens

Metastasis-associated protein MTA3 is a protein that in humans is encoded by the MTA3 gene. MTA3 protein localizes in the nucleus as well as in other cellular compartments MTA3 is a component of the nucleosome remodeling and deacetylate (NuRD) complex and participates in gene expression. The expression pattern of MTA3 is opposite to that of MTA1 and MTA2 during mammary gland tumorigenesis. However, MTA3 is also overexpressed in a variety of human cancers.

<span class="mw-page-title-main">CEACAM5</span> Mammalian protein found in Homo sapiens

Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) also known as CD66e, is a member of the carcinoembryonic antigen (CEA) gene family.

The MRN complex is a protein complex consisting of Mre11, Rad50 and Nbs1. In eukaryotes, the MRN/X complex plays an important role in the initial processing of double-strand DNA breaks prior to repair by homologous recombination or non-homologous end joining. The MRN complex binds avidly to double-strand breaks both in vitro and in vivo and may serve to tether broken ends prior to repair by non-homologous end joining or to initiate DNA end resection prior to repair by homologous recombination. The MRN complex also participates in activating the checkpoint kinase ATM in response to DNA damage. Production of short single-strand oligonucleotides by Mre11 endonuclease activity has been implicated in ATM activation by the MRN complex.

Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Endotoxins most commonly refer to the lipopolysaccharide (LPS) or lipooligosaccharide (LOS) that are in the outer plasma membrane of Gram-negative bacteria. The botulinum toxin, which is primarily produced by Clostridium botulinum and less frequently by other Clostridium species, is the most toxic substance known in the world. However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxins. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.

<span class="mw-page-title-main">Metastatic breast cancer</span> Type of cancer

Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumors, secondaries or stage IV breast cancer, is a stage of breast cancer where the breast cancer cells have spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer; there is no stage after IV.

mir-145 Non-coding RNA in the species Homo sapiens

In molecular biology, mir-145 microRNA is a short RNA molecule that in humans is encoded by the MIR145 gene. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

<span class="mw-page-title-main">Joan Massagué</span> Spanish biologist

Joan Massagué, is a Spanish biologist and the current director of the Sloan Kettering Institute at Memorial Sloan Kettering Cancer Center. He is also an internationally recognized leader in the study of both cancer metastasis and growth factors that regulate cell behavior, as well as a professor at the Weill Cornell Graduate School of Medical Sciences.

<span class="mw-page-title-main">Cancer biomarker</span> Substance or process that is indicative of the presence of cancer in the body

A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. Genetic, epigenetic, proteomic, glycomic, and imaging biomarkers can be used for cancer diagnosis, prognosis, and epidemiology. Ideally, such biomarkers can be assayed in non-invasively collected biofluids like blood or serum.

<span class="mw-page-title-main">Tumor microenvironment</span> Surroundings of tumors including nearby cells and blood vessels

The tumor microenvironment is a complex ecosystem surrounding a tumor, composed of cancer cells, stromal tissue and the extracellular matrix. Mutual interaction between cancer cells and the different components of the tumor microenvironment support its growth and invasion in healthy tissues which correlates with tumor resistance to current treatments and poor prognosis. The tumor microenvironment is in constant change because of the tumor's ability to influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.

References

  1. ↑ Hammond NG, Scullard HH (1970). The Oxford classical dictionary (Second ed.). Oxford. ISBN   978-0198691174. OCLC   102949.{{cite book}}: CS1 maint: location missing publisher (link)
  2. ↑ Calabrese V, Mancuso C, Calvani M, Rizzarelli E, Butterfield DA, Stella AM (October 2007). "Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity". Nature Reviews. Neuroscience. 8 (10): 766–75. doi: 10.1038/nrn2214 . PMID   17882254.
  3. ↑ "A Receptor-Mediated Pathway for Cholesterol Homeostasis". Joseph L. Goldstein Nobel Lecture. The Nobel Foundation.
  4. ↑ Ghavami S, Chitayat S, Hashemi M, Eshraghi M, Chazin WJ, Halayko AJ, Kerkhoff C (December 2009). "S100A8/A9: a Janus-faced molecule in cancer therapy and tumorgenesis". European Journal of Pharmacology. 625 (1–3): 73–83. doi:10.1016/j.ejphar.2009.08.044. PMID   19835859.
  5. ↑ Tímár J, Lapis K, Dudás J, Sebestyén A, Kopper L, Kovalszky I (June 2002). "Proteoglycans and tumor progression: Janus-faced molecules with contradictory functions in cancer". Seminars in Cancer Biology. 12 (3): 173–86. doi:10.1016/S1044-579X(02)00021-4. PMID   12083848.
  6. ↑ Zhuang X, Zhang H, Li X, Li X, Cong M, Peng F, et al. (October 2017). "Differential effects on lung and bone metastasis of breast cancer by Wnt signalling inhibitor DKK1". Nature Cell Biology. 19 (10): 1274–1285. doi:10.1038/ncb3613. PMID   28892080. S2CID   36525770.
  7. ↑ Stern D, Weisemann J, Le Blanc A, von Berg L, Mahrhold S, Piesker J, et al. (May 2018). "A lipid-binding loop of botulinum neurotoxin serotypes B, DC and G is an essential feature to confer their exquisite potency". PLOS Pathogens. 14 (5): e1007048. doi: 10.1371/journal.ppat.1007048 . PMC   5951583 . PMID   29718991.
  8. ↑ "Synthetic molecule invades double-stranded DNA". EurekAlert!. Retrieved 2019-12-05.
  9. ↑ "Two-Faced Molecule Slips between DNA Strands". GEN - Genetic Engineering and Biotechnology News. 2018-11-15. Retrieved 2019-12-05.
  10. ↑ Edite Bezerra da Rocha, Maria; Freire, Francisco da Chagas Oliveira; Erlan Feitosa Maia, Fábio; Izabel Florindo Guedes, Maria; Rondina, Davide (February 2014). "Mycotoxins and their effects on human and animal health". Food Control. 36 (1): 159–165. doi:10.1016/j.foodcont.2013.08.021.
  11. ↑ Banfalvi, Gaspar (2021-11-15). "Janus-Faced Molecules against Plant Pathogenic Fungi". International Journal of Molecular Sciences. 22 (22): 12323. doi: 10.3390/ijms222212323 . ISSN   1422-0067. PMC   8623416 . PMID   34830204.
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