Integrins comprise a large family of αβ heterodimeric cell-surface receptors that mediate diverse processes involved in cell-cell and cell-matrix interactions such as cellular adhesion and migration, cell survival and differentiation. It is now well documented that integrins play a crucial role in cancer metastasis and angiogenesis. The β3 integrins appear to have an important stimulatory role in tumour progression and metastasis and, thus, have been often proposed as potential targets for cancer diagnosis and therapy. In this study, we evaluated the in vitro and in vivo properties of B16 mouse melanoma cells with low expression of integrin β3. Proliferation rate, adhesive properties and the ability to migrate and metastasize were studied. Over 90% inhibition of integrin β3 expression was achieved as a result of the transfection with siRNA. No changes in the proliferation rate were observed in siRNA-transfected B16 cells; however, they showed impaired ability to bind to fibronectin. Moreover, inhibition of integrin β3 expression caused almost complete impairment of the ability of B16 cells to migrate through matrigel and metastasize. The mean number of lung metastatic colonies in mice inoculated intravenously with B16 expressing low levels of integrin β3 was decreased to 14 colonies compared to 101 in the control group. These results provide evidence for a direct role of integrin β3 in the adhesion, migration and metastasis processes of mouse melanoma cells and point to the potential therapeutic advantages of siRNAs.
This study examines the synthesis and cytostatic activity of new 5,6-dimethyl-1-substituted-6H-pyrido[4,3-b]carbazole derivatives. Their structures were confirmed by (1)H-NMR and elemental analysis. Seven of the new compounds were tested by the SRB method in vitro against human lung cancer (A549) and human kidney cancer (A498) cell lines. Biological tests indicated remarkable cytostatic effects of four compounds tested in comparison with ellipticine and cisplatin as reference drugs. One particular compound 3c was about four times more active on A498 than ellipticine with similar activity on the A549 cell line, and outperformed cisplatin activity on both tumor cell lines.
A novel set of S16020 derivatives was designed applying structure-activity relationships (SAR). The newly synthesized compounds were subjected to in vitro cytostatic activity screening against human kidney cancer (cell line A498), human lung cancer (cell line A549) and normal human dermal fibroblasts (cell line NHDF). Two 6H-pyrido [4,3-b]carbazole derivatives exhibited stronger potency against both investigated cell lines than the reference compounds ellipticine and doxorubicin.
Fused pyridine derivatives R 0450Synthesis and Anticancer Activity of New 1-Substituted-6H-pyrido[4,3-b]carbazole Derivatives. -7 Title compounds of type (VI), (VII), and (IX) are tested against human lung cancer (A549) and human kidney cancer (A498) cell lines. Especially (VII) shows good activity, comparable to that of ellipticine and with higher activity than cisplatin. -(TYLINSKA*, B.; JASZTOLD-HOWORKO, R.; MASTALARZ, H.; SZCZAURSKA-NOWAK, K.; WIETRZYK, J.; Arch. Pharm. (Weinheim, Ger.) 341 (2008) 6, 351-356; Dep. Org. Chem., Fac. Pharm., Wroclaw Univ. Med., PL-50-137 Wroclaw, Pol.; Eng.) -M. Bohle 41-158
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