Citrus flavone tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes.

Tangeritin (citrus) hợp chất kháng HL60

From Wikipedia, the free encyclopedia

Tangeritin (Tangeretin)

Names
IUPAC name 5,6,7,8-tetramethoxy-2-(4-methoxyphenyl)-4H-1-benzopyran-4-one
Identifiers
CAS Number	481-53-8
3D model (JSmol)	Interactive image
ChEBI	CHEBI:9400
ChemSpider	61389
ECHA InfoCard	100.006.883
EC Number	207-570-1
KEGG	C10190
PubChem CID	68077
UNII	I4TLA1DLX6
InChI[show]
SMILES[show]
Properties
Chemical formula	C20H20O7
Molar mass	372.37 g/mol
Density	1.244 ± 0.06 g/cm3[1]
Melting point	155 to 156 °C (311 to 313 °F; 428 to 429 K)
Boiling point	565.3 ± 50.0 °C (1,049.5 ± 90.0 °F; 838.4 ± 50.0 K)[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Tangeritin is an O-polymethoxylated flavone that is found in tangerine and other citrus peels. Tangeritin strengthens the cell wall and acts as a plant's defensive mechanism against disease-causing pathogens.^[2]

It has also been used as a marker compound to detect contamination in citrus juices.^[2]

Although few randomized, double-blind human studies have been done, animal research shows the potential of tangeritin as a cholesterol lowering agent.^[3] A study on rats demonstrated potential protective effects against Parkinson's disease.^[4]

Tangeritin also shows enormous potential as an anti cancer agent. In in vitro studies, tangeritin appears to counteract some of the adaptations of cancer cells. Tangeritin induced apoptosis in leukemia cells while sparing normal cells.^[5] In a study on two human breast cancer cell lines and one colon cancer cell line, tangeritin blocked cell cycle progression at the G1 (growth) phase in all three cell lines, without inducing apoptosis in the tumor cell lines. Once tangeritin was removed from the tumor cells, their cell cycle progression returned to normal.^[6] Tangeritin also counteracts tumor suppression of gap junction intercellular signaling.^[7] In summary, in vitro studies show antimutagenic,^[8] antiinvasive^[9] and antiproliferative^[10] effects. One caveat is that tangeritin appears to counteract the anticancer drug tamoxifen and to suppress the activity of natural killer cells.^[11] H

The following is a list of methods used to extract tangeritin from citrus peels:

• column chromatography
• preparative-high performance liquid chromatography
• super critical fluid chromatography
• high speed counter current chromatography
• a combination of vacuum flash silica gel chromatography and flash C₈ column chromatography
• flash chromatography

However, methods for tangeritin extraction are currently being tested to maximize efficiency and percent yields as its uses in treatment of cancer and other diseases are becoming better understood.^[2]

Tangeritin is commercially available as a dietary supplement.

Shearinine kháng HL60

From Wikipedia, the free encyclopedia

Shearinines A,D,E,and F

Shearinines A,D,E,and F, are marine fungal isolates with anticancer activity in vitro. They were isolated from a stain of Penicillium janthinellum Biourge. Their potential anticancer activity has been suggested by their induction of apoptosis in HL-60 cells.^[1] Shearinines D, E and G have also been found to block activity on large-conductance calcium-activated potassium channels.^[2]

Clostridium perfringens beta toxin kháng HL60

From Wikipedia, the free encyclopedia

Clostridium perfringens
Photomicrograph of Clostridium perfringens.
Scientific classification
Domain:	Bacteria
Phylum:	Firmicutes
Class:	Clostridia
Order:	Clostridiales
Family:	Clostridiaceae
Genus:	Clostridium
Species:	C. perfringens
Binomial name
Clostridium perfringens Veillon & Zuber 1898

Clostridium perfringens beta toxin is one of the four major lethal toxins produced by Clostridium perfringens Type B and Type C strains.^[1] It is a necrotizing agent and it induces hypertension by release of catecholamine. It has been shown to cause necrotic enteritis in mammals and induces necrotizing intestinal lesions in the rabbit ileal loop model.^[2] C. perfringens beta toxin is susceptible to breakdown by proteolytic enzymes, particularly trypsin.^[3] Beta toxin is therefore highly lethal to infant mammals because of trypsin inhibitors present in the colostrum.^[3]

Contents

  [hide] 

• 1Structure and homology
• 2Function
  • 2.1Pore formation
• 3Clinical significance
  • 3.1C. perfringens Type B
  • 3.2C. perfringens Type C
• 4See also
• 5References

Structure and homology[edit]

Clostridium perfringens beta toxin shows significant genetic homology with several other toxins. C. perfringens beta toxin shows 28% homology with S. aureus alpha toxin and similar homology to S. aureus gamma-toxin and leukocidin. It appears in two forms. The smaller, with a molecular mass of 34 kDa, represents the monomeric gene product. The larger has a molecular mass of 118 kDa and may be an oligomer of smaller units. The first 27 amino acids may encode a signal that allows beta toxin to cross the cell membrane, further evidenced by the presence of beta toxin in extracellular fluid of C. perfringens cultures.^[4]

Function[edit]

Pore formation[edit]

Because C. perfringens beta toxin shares homology with S. aureus pore-forming alpha toxin, it was hypothesized that beta toxin acts in a similar way. Upon investigation, it was found that C. perfringens beta toxin forms cation-selective pores in cell membranes^[5] of 1.6–1.8 nm^[6] and results in swelling and lysis in HL60 cells.^[7] Treatment of these cells with beta toxin induces and efflux K⁺ and influxes of Ca²⁺, Cl⁻ and Na⁺.^[7] Heat-stable beta-toxin oligomers are shown to bind to cell membranes of human umbilical vein endothelial cells; endothelial cells are beta toxin's primary target, upon introduction.^[5] Further work on beta toxin has been hampered by its ineffectiveness on many readily available cell lines.^[5][7]

Clinical significance[edit]

C. perfringens Type B[edit]

Beta toxin is the principal disease causing toxin in C. perfringens type B infection. Type B has caused lamb dysentery in Great Britain and South Africa.^[8] Enterotoximia caused by a strains of Type B has been seen in foals in Great Britain and sheep and goats in Iran.^[8] Vaccines have been developed to combat lamb dysentery in sheep flocks at high risk.^[8]

C. perfringens Type C[edit]

Beta toxin from C. perfringens type C is highly lethal to neonatal pigs and occurs worldwide in farmed pigs.

Beta toxin is the principal disease causing toxin in C. perfringens type C infection, and causes necrotizing enteritis and enterocolitis. In the disease process, C. perfringens penetrates the upper jejunum between absorptive cells and releases beta toxin. Beta toxin causes necrosis of the villi and mucosa, often causing blood loss into the lumen and intestinal wall.^[9] Type C causes fatal hemorrhagic enteritis in neonatal calves in North America^[8] but has been particularly prevalent in swine worldwide.^[10] It is primarily fatal to animals 1–3 days old, whose digestive enzymes may not be sufficiently active to break down beta toxin. It has been experimentally shown that trypsin may normally break down beta toxin, and trypsin shortages in the digestive system of experimental animals have been used to induce type C disease. Vaccination of pregnant sows has proven effective at preventing the disease in piglets.^[9][10] Outbreaks in piglets from unvaccinated sows may be treated with oral antibiotics and antiserum.^[9]

Cytotrienin A hợp chất kháng HL60

From Wikipedia, the free encyclopedia

The structure of Cytotrienin A.

Cytotrienin A (Cyt A) is a secondary metabolite isolated from Streptomyces sp. RK95-74 isolated from soil in Japan in 1997.^[1][2] Cyt A is an ansamycin.^[2] Cytotrienin A induces apoptosis on HL-60 cells, as well as inhibiting translation in eukaryotes by inhibiting eukaryotic elongation factor 1A (eEF1A), which can act as an oncogene.^[1][3] These functions lead to the potential of the microbial metabolite acting as an anticancer agent, specifically for blood cancers, as it has proved to be more effective with leukemic cell lines.^[1][3] Cyt A is thought to induce apoptosis by activating c-Jun N-terminal Kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and p36 myelin basic protein (MBP) kinase.^[3][4]

Structure[edit]

Cytotrienin A is an ansamycin with a macrocyclic, twenty-one carbon, lactam, featuring an E,E,E-triene and an unsual aminocyclopropane carboxylic acid side chain.^[2]The structure features four stereocenters, 3 of which are contiguous. The absolute stereochemistry of the naturally occurring metabolite revealed it to be (+)-Cytotrienin A.^[2]

Biology and Biochemistry[edit]

Cytotrienin A has a median effective dose value of 7.7 nM to induce apoptosis on HL-60 cells.^[1] It was also shown that the metabolite has greater growth inhibitory activity on HL-60 cells at low concentrations and little impact on non-tumorous cells, while at high concentrations the reverse relationship was seen.^[1] The apoptosis pathway was shown to involve the proteolytic activation of MST/Krs proteins by caspase-3 which results in the activation of p36 MBP kinase through the creation of ROS. The concentrations needed to induce this pathway were found to be the same required to induce apoptosis on HL-60 cells.^[4][5] Cyt A also activates c-Jun N-terminal kinase, and its apoptotic effects are inhibited by dominant negative c-Jun. While the presence of inactive MST/Krs proteins and dominant negative c-Jun completely inhibited apoptosis.^[4]

Additionally, cytotrienin A acts to inhibit eEF-1A, and thus inhibiting translation. This can make the tumor less effective at producing anti-apoptotic mediators and lowering the tumor's drug resistance.^[3] The translation inhibition is thought to occur before apoptosis can be detected. Inhibition of HUVEC tube formation was also shown, which indicates an inhibition of angiogenesis and further evidence of its anti-cancer potential.^[3] In A549 cells, where cytotrienin A has been shown to be less effective, cyt A inhibits the expression of ICAM-1. This occurs when the TNF receptor 1 is shredded through the activation of extracellular signal-regulated kinase (ERK) and p38 MAPK.^[3][6] Cyt A inhibited ICAM-1 expression by TNF-α and IL-1α at similar concentrations, but was found to be inhibited by TAPI-2, an inhibitor to the TNF-α-converting enzyme (TACE).^[6]