Abstract
We previously reported that smenospongine, a sesquiterpene aminoquinone isolated from the marine sponge Dactylospongia elegans, showed antiproliferative or cytotoxic activities on leukemia cells. In this study, we investigated the effect of smenospongine on solid tumors. Since angiogenesis is well known to be closely involved in growth and metastasis of solid tumors, the antiangiogenic effect of smenospongine was determined. We found that smenospongine inhibited proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVEC). Moreover, the inhibitory activity of smenospongine on growth of solid tumor cells was investigated. Smenospongine inhibited the growth of 39 human solid cancer cells in vitro, with a mean Log GI50 value of −5.55. In conclusion, smenospongine exhibits antitumor activity on solid tumors via two mechanisms, an antiangiogenic effect on endothelial cells and direct inhibition of growth of tumor cells.
Highlights
Angiogenesis, the process of generating new blood vessels from a primitive vascular network, is known to be required for the growth and metastasis of solid tumors
We previously reported that smenospongine (Figure 1), a sesquiterpene aminoquinone isolated from the Indonesian marine sponge Dactylospongia elegans, showed multifaceted antitumor activities on leukemia cells [4,5,6]
To examine the antiangiogenic activity of smenospongine, we first determined the activity on the proliferation of human umbilical vein endothelial cells (HUVEC) by use of WST-8 assay as reported by us previously [3]
Summary
Angiogenesis, the process of generating new blood vessels from a primitive vascular network, is known to be required for the growth and metastasis of solid tumors. Antiangiogenesis has become known as an effective approach for therapy of solid tumors. Approval of avastin in 2004 (a recombinant human monoclonal antibody against VEGF), more than 30 inhibitors of angiogenesis have been either approved or are in clinical trials for cancer therapy [1,2,3]. Smenospongine induced G1 arrest in chronic myelogenous leukemia (CML) cells and apoptosis in acute myelogenous leukemia (AML) and lymphocytic leukemia [4,6]. We present our investigations of the effect of smenospongine on solid tumors with a focus on the antiangiogenic effect. The inhibitory effect on the growth of various cancer cells is examined
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