Cucurbitacin E is a biochemical compound from the family of

cucurbitacin Cucurbitacins are a class of biochemistry, biochemical compounds that some plants – notably members of the pumpkin and gourd family, Cucurbitaceae – produce and which function as a defense against herbivores. Cucurbitacins and their deriva ...

s. These are found in plants which are member of the family

Cucurbitaceae The Cucurbitaceae (), also called cucurbits or the gourd family, are a plant family (biology), family consisting of about 965 species in 101 genera.

, most of them coming from traditional Chinese medicinal plants, but also in other plants such as pumpkins and gourds. Cucurbitacin E is a highly oxidated

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

consisting of a tetracyclic

triterpene Triterpenes are a class of terpenes composed of six isoprene units with the molecular formula C30H48; they may also be thought of as consisting of three terpene units. Animals, plants and fungi all produce triterpenes, including squalene, the pre ...

. Specific modifications in this molecule under certain conditions can form other types of cucurbitacins such as cucurbitacin I, J, K and L. , it is being investigated for its potential biological effects. Cucurbitacin E has been found to increase activity of anti-cancer drugs in certain types of cancers. It selectively increases chemosensitivity of nutrient receptors, on or inside cancer cells, to anti-cancer drug molecules, thereby decreasing binding of the nutrients to cancer cells, and decreasing their growth, leading to selective cell death of cancer cells. Cogombre

Research

Anti-inflammatory

Cucurbitacin E anti-inflammatory activities are proved in vivo and in vitro. It is useful in the treatment of inflammation because of the inhibition of

cyclooxygenase Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for biosynthesis of prostanoids, including thromboxane and prostaglandins such a ...

and

reactive nitrogen species Reactive nitrogen species (RNS) are a family of antimicrobial molecules derived from nitric oxide (•NO) and superoxide (O2•−) produced via the enzymatic activity of inducible nitric oxide synthase 2 (Nitric oxide synthase 2A, NOS2) and NADPH ...

(RNS) but not

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

(ROS).

Macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

s are responsible for the production of various cytokines, RNS and ROS, growth factors and

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addit ...

s as a response to activation signal such as chemical mediators, cytokines and

lipopolysaccharide Lipopolysaccharide (LPS), now more commonly known as endotoxin, is a collective term for components of the outermost membrane of the cell envelope of gram-negative bacteria, such as '' E. coli'' and ''Salmonella'' with a common structural archit ...

. Although these molecules have an important role, they can also have damaging effects, like some RNS. Cucurbitacin possesses dose-dependent anti-inflammatory activity related to its inhibition of

nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...

(an RNS) production in macrophages without affecting the viability of these cells. As cucurbitacin E doesn't affect normal human liver cells, it may have therapeutic potential and effective treatment for a variety of inflammation mediated diseases.

Antioxidant

Cucurbitacin E glycoside has demonstrated

antioxidant Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...

and free-radical scavenging properties. Its antioxidant and free-radical scavenging properties were measured by the ability of cucurbitacin glycoside combination (CGC), a combination of cucurbitacin B and E glycosides, to reduce

ABTS In biochemistry, ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) is a chemical compound used to observe the reaction kinetics of specific enzymes. A common use for it is in the enzyme-linked immunosorbent assay (ELISA) to detect the ...

cation to its original form and also the capacity to inhibit MDA formation originated in the oxidation of

linoleic acid Linoleic acid (LA) is an organic compound with the formula . Both alkene groups () are ''cis''. It is a fatty acid sometimes denoted 18:2 (n−6) or 18:2 ''cis''-9,12. A linoleate is a salt or ester of this acid. Linoleic acid is a polyunsat ...

. Using electron paramagnetic resonance, it was confirmed that CGC had antioxidant properties because of its capacity for scavenging free radicals, such as: superoxide anion (O2-), hydroxyl radical (OH-) and singlet oxygen. Not all natural antioxidants have strong free-radical scavenging properties against multiple free-radicals. CGC is being investigated as a treatment for human diseases that are linked to oxidative or free-radical damage such as atherosclerosis, cancer, Alzheimer's disease and diabetes.

Cytostatic

Cucurbitacin E is an inhibitor during the S to M phase in the cell mitosis. It causes a reduction of cell multiplication.

Cytotoxicity

This triterpene can inhibit the

phosphorylation In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...

of the

cofilin ADF/cofilin is a family of actin-binding proteins associated with the rapid depolymerization of Actin, actin microfilaments that give actin its characteristic dynamic instability. This dynamic instability is central to actin's role in muscle cont ...

protein, a family of actin-binding proteins that disassembles actin filaments. Cucurbitacin E shows cytotoxicity to: * The colon cancer cell line HCT-116 * The lung cancer cell line

NCI-H460 The NCI-60 cancer cell line panel is a group of 60 human cancer cell lines used by the National Cancer Institute (NCI) for the screening of compounds to detect potential anticancer activity. Purpose The screening procedure is called the NCI-6 ...

* The breast cancer cell lines

MCF-7 MCF-7 is a breast cancer cell line isolated in 1970 from a 69-year-old woman. MCF-7 is the acronym of Michigan Cancer Foundation-7, referring to the institute in Detroit where the cell line was established in 1973 by Herbert Soule and co-workers ...

and ZR-75-1 * The central nervous system tumor cell line SF-268 * The oral epidermoid carcinoma cell line KB * The cervical cancer cell line

HeLa HeLa () is an immortalized cell line used in scientific research. It is the oldest human cell line and one of the most commonly used. HeLa cells are durable and prolific, allowing for extensive applications in scientific study. The line is ...

* The fibrosarcoma cell line

HT1080 HT1080 is a fibrosarcoma cell line which has been used extensively in biomedical research. The cell line was created from tissue taken in a biopsy of a fibrosarcoma present in a 35-year-old human male. The patient who supplied the sample had not u ...

* The acute leukemia cell lines U937 and

HL-60 The HL-60 cell line is a human leukemia cell line that has been used for laboratory research on blood cell formation and physiology. HL-60 proliferates continuously in suspension culture in nutrient and antibiotic chemicals. The doubling time is ab ...

* The prostate cancer cell lines PC,

LNCaP LNCaP cells are a cell line of human cells commonly used in the field of oncology. LNCaP cells are androgen-sensitive human prostate adenocarcinoma cells derived from the left supraclavicular lymph node metastasis from a 50-year-old caucasian ma ...

and

DU145 DU145 (DU-145) is a human prostate cancer cell line. DU145, PC3, and LNCaP are considered to be the standard prostate cancer cell lines used in therapeutic research. The DU145 cell line was derived from a central nervous system metastasis, of p ...

* The pancreatic cancer cell line Panc-1 * The ovarian cancer cell line S-2 * The bladder cancer cell line T24 * The hepatic carcinoma cell lines BEL-7402 and

HepG2 Hep G2 (or HepG2) is a human liver cancer cell line. Hep G2 is an immortal cell line which was derived in 1975 from the liver tissue of a 15-year-old Caucasian male from Argentina with a well-differentiated hepatocellular carcinoma. ...

Anti-angiogenesis

Cucurbitacin can also inhibit

VEGFR2 Kinase insert domain receptor (KDR, a type IV receptor tyrosine kinase) also known as vascular endothelial growth factor receptor 2 (VEGFR-2) is a VEGF receptor. ''KDR'' is the human gene encoding it. KDR has also been designated as CD309 (cluster ...

-mediated Jak-STAT3 and MAPK signaling pathways. Anti-angiogenesis property of cucurbitacin E was demonstrated in vitro but also in vivo in a chick embryo

chorioallantoic membrane The chorioallantoic membrane (CAM), also known as the chorioallantois, is a highly vascularized membrane found in the eggs of certain amniotes like birds and reptiles. It is formed by the fusion of the mesodermal layers of two extra-embryonic memb ...

and in a mouse corneal angiogenesis model.

Anti-invasion and anti-metastasis

In vitro, cucurbitacin E inhibits the adhesion of cancer cells in type I collagen.

Hepatoprotecive effect

In vitro, cucurbitacin E protects hepatocytes from CCl₄ (

carbon tetrachloride Carbon tetrachloride, also known by many other names (such as carbon tet for short and tetrachloromethane, also IUPAC nomenclature of inorganic chemistry, recognised by the IUPAC), is a chemical compound with the chemical formula CCl4. It is a n ...

), by reducing GPT, GOT, ALP, TP and TBIL serums.

Insecticide

Curcurbitacin E has insecticidal effects against the aphid ''

Aphis craccivora ''Aphis craccivora'', variously known as the cowpea aphid, groundnut aphid or black legume aphid, is a true bug in the family ''Aphididae''. Originally of probable Palearctic origin, it is now an invasive species of cosmopolitan distribution. ...

''.Torkey, H.M., Abou-Yousef, H.M., Abdel Azeiz, A.Z. and Hoda, E.A. Farid. Insecticidal Effect of Cucurbitacin E Glycoside Isolated from Citrullus colocynthis Against Aphis craccivora. Australian Journal of Basic and Applied Sciences 2009; 3(4): 4060-4066

References

External links

* http://www.chemicalbook.com/ChemicalProductProperty_EN_CB3372306.htm * https://web.archive.org/web/20120426084358/http://home.ncifcrf.gov/mtdp/Catalog/compounds/106399.html * http://www.chemblink.com/products/18444-66-1.htm