Inhibition of epidermoid carcinoma A431 cell growth and angiogenesis in nude mice by early and late treatment with a novel dextran derivative

Abstract

We investigated the effect of a new dextran derivative, phenylacetate carboxymethyl benzylamide dextran (NaPaC), on epidermoid carcinoma A431 cells secreting a large quantity of angiogenic factor, vascular endothelial growth factor (VEGF). In vitro, NaPaC inhibited the proliferation of A431 cells (IC 50 ¼ 5 mM). Also, NaPaC decreased the binding of radiolabelled VEGF 165 to endothelial cells (IC 50 ¼ 0.2 mM). In vivo, we explored the effects of NaPaC (15 mg kg À1 ) on A431 xenograft growth starting the drug administration at the time of tumour cell inoculation (early treatment) and 1 week later, when tumours were well established (late treatment). Early treatment was more efficient on tumour inhibition (70% vs control) than late treatment (50% vs control). Early and late NaPaC-treatment increased the aponecrosis in tumour by 70 and 30%, respectively. Whatever treatment, NaPaC inhibited the intratumour endothelial cell density in the same manner. In contrast, vessel area was decreased only when NaPaC was injected early (35%). These results show that NaPaC has a potent inhibitory effect, dependent on treatment outset, on epidermoid carcinoma growth associated with an intratumour microvascular network diminution and an aponecrosis increase. As this drug is nontoxic at efficient dose, it offers interesting perspectives for the therapy of malignant lesions.

Apoptosis shifts to necrosis via intermediate types of cell death by a mechanism depending on c- myc and bcl-2 expression

“…The results obtained have allowed the effect of chemical hypoxia to be superimposed on the detection of aponecrosis by TEM analysis. Recently, the occurrence of aponecrosis as a mixed form of cell death sharing apoptosis and necrosis has been described in rat hepatocytes (Cheng et al 2003a(Cheng et al , 2003b and in an epidermoid carcinoma (Di Benedetto et al 2003). Furthermore, the same morphology of dying cells has been described as necrapoptosis by other authors (Kim el al.…”

In vivo pulsed magneto-motive ultrasound imaging using high-performance magnetoactive contrast nanoagents

“…Cells (1.2×10 6 ) suspended in 0.2 ml 1x PBS (Sigma Aldrich, USA) were inoculated subcutaneously on the right flank of the mice. 25, 26 After 18 days, the volume of the implanted tumors reached to 8 to 10 mm in diameter. All these procedures were performed under the animal protocol approved by Institutional Animal Care and Use Committee (IACUC) at The University of Texas at Austin.…”

A new dimethyl ester bisphosphonate inhibits angiogenesis and growth of human epidermoid carcinoma xenograft in nude mice

“…To visualize intratumor endothelial cells (ECs), sections of 5 mm were specifically stained with GSL-1 lectin (Vector, Burlingame, California, USA) as previously described [17][18][19]. To visualize intratumor endothelial cells (ECs), sections of 5 mm were specifically stained with GSL-1 lectin (Vector, Burlingame, California, USA) as previously described [17][18][19].…”

“…Image analysis was performed using the Image analysis NIH program as previously described [17][18][19]. Image analysis was performed using the Image analysis NIH program as previously described [17][18][19].…”