Antiangiogenic potential of camptothecin and topotecan

Abstract

In this work we showed that CPT and TPT inhibit human endothelial cell growth in vitro in a non-cytotoxic manner and that this inhibition lasts more than 96 h after drug removal. We also showed that LCPT and TPT, unlike a nonspecific cytotoxic agent, cisplatin, are as effective as TNP-470 in inhibiting angiogenic growth in the in vivo disc angiogenesis model. From this observation we propose that in addition to their proven tumoricidal activities, camptothecins may have an indirect in vivo antitumor effect mediated through the inhibition of angiogenesis.

Butyrate-induced proapoptotic and antiangiogenic pathways in EAT cells require activation of CAD and downregulation of VEGF

“…The immunohistological studies clearly show the inhibition of blood vessel formation in H&E staining and CD31 analysis, and thus suggest that BuA primarily acts on endothelial cells, and hence inhibition of angiogenesis. The biphasic effect of BuA as proapoptotic and antiangiogenic compound is consistent with those of some other anticancer drugs [43,44] such as cyclophosphamide [45], and campothecin [46,47], thus strongly suggesting that these kinds of anti-tumor compounds seem to be more promising in clinical practice than the compounds that directly target angiogenesis.…”

Topotecan inhibits VEGF‐ and bFGF‐induced vascular endothelial cell migration via downregulation of the PI3K‐Akt signaling pathway

“…A recent report documented that topotecan inhibited angiogenic growth in the in vivo rat disc angiogenesis model and was as effective as the potent angiogenic inhibitor TNP470. 12 Similar results have also been reported in a mouse cornea angiogenesis model in vivo. 13 In our study, we investigated the molecular mechanisms of the antiangiogenic effects of topotecan.…”

Electroporation of human microvascular endothelial cells: evidence for an anti-vascular mechanism of electrochemotherapy

“…In comparison to the IC 50 values for several human and murine tumour cell lines, treated with either of these drugs (Tables 1 and 2), the values for HMEC-1 cells appear relatively resistant, especially to cisplatin (Lazo et al, 1989;Hait et al, 1994;Kambe et al, 1996;Dirix et al, 1997;Cemazar et al, 1998a,b). This is consistent with a report of relatively little antivascular action of cisplatin in vivo (Clements et al, 1999). In contrast, the present result for bleomycin indicates that HMEC-1 cells show an equal, or enhanced, sensitivity to that reported for tumour cells with the maximum value of ˜2 00-fold more sensitive than tumour cell lines (Table 2) (Hait et al, 1994;Dirix et al, 1997;Cemazar et al, 1998a).…”