Experimental anti-cancer synthetic molecule targets tumor cell growth and angiogenesis

Jun 18, 2008

A recent study conducted by three French CNRS (Centre National de la Recherche Scientifique) laboratories describes a new candidate anti-cancer drug, named HB-19. In contrast to conventional anti-cancer drugs, HB-19 has a dual mechanism of action by its capacity to target independently both tumor cell growth, as well as tumor angiogenesis (formation of new blood vessels which bring necessary nutrients and oxygen to the tumor mass). The molecular target of HB-19 is nucleolin expressed on the surface of all activated cells, in particular rapidly growing tumor cells and endothelial cells that play a key role in angiogenesis. The results of this work, directed by Ara Hovanessian, are published in the June 18 edition of PLoS ONE.

Nucleolin is one of the major proteins of the nucleus, but it is also expressed on the cell surface where it serves as a binding protein for variety of ligands implicated in cell proliferation, differentiation, adhesion, mitogenesis and angiogenesis. The specific binding of HB-19 to surface-expressed nucleolin leads to internalization of the complex followed by degradation of this multifunctional protein.

Using various in vitro and in vivo experimental models, the authors show that HB-19 is a potent inhibitor of tumor cell growth and angiogenesis. In mice grafted with human breast tumor cells, HB-19 treatment markedly suppresses the progression of tumor development, and in some cases eliminates measurable tumors while displaying no toxicity to normal tissue.

The in vivo antitumoral action of HB-19 in this mouse model (i.e. inhibition of tumor development) is comparable to that of 5-fluorouracil, a drug that is used to treat several types of human cancer. However, 5-fluorouracil has toxic effects on circulating white blood cells whereas HB-19 treatment demonstrated no observable toxicity in this study. Another possible advantage of HB-19 over existing anti-cancer drugs is its reproducible synthesis by conventional techniques to generate a stable product that is readily soluble in physiological solutions.

The direct action of HB-19 on tumor growth and angiogenesis fulfills the criteria for an efficient anticancer drug, since combination therapy targeting both of these events is considered an optimal strategy in cancer management. In view of such dual inhibitory action, reproducible synthesis, high stability, selective tissue retention, and in vivo lack of toxicity, HB-19 may be a promising candidate for evaluation in future clinical trials.

Source: Public Library of Science

Explore further: Research demonstrates potential method to better control lung cancer using radiotherapy

add to favorites email to friend print save as pdf

Related Stories

Airlines on alert as eruption begins in Iceland

11 hours ago

Iceland's Bardarbunga volcano burst forth with a small eruption Saturday under the ice of Europe's largest glacier, scientists said, prompting the country to close airspace over the area.

Two Galileo satellites lose their way

14 hours ago

Two European Galileo satellites launched as part of a navigation system designed to rival GPS have failed to locate their intended orbit, launch firm Arianespace said Saturday.

Volcanic eruption begins under Iceland glacier

14 hours ago

Iceland's Bardarbunga volcano began erupting Saturday under the country's largest glacier after a week of seismic activity rattled the area with thousands of earthquakes, the country's Meteorological Office ...

Recommended for you

Fewer die from colorectal cancer

53 minutes ago

Patients with intestinal polyps have a lower risk of dying from cancer than previously thought, according to Norwegian researchers.

Better classification to improve treatments for breast cancer

13 hours ago

Breast cancer can be classified into ten different subtypes, and scientists have developed a tool to identify which is which. The research, published in the journal Genome Biology, could improve treatments and targeting of tre ...

Risk of diabetes up in hodgkin's lymphoma survivors

15 hours ago

(HealthDay)—Para-aortic radiation correlates with increased diabetes mellitus (DM) risk for Hodgkin's lymphoma (HL) survivors, according to a study published online Aug. 25 in the Journal of Clinical On ...

User comments : 0