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Abstract

We have investigated the effect of calcium spirulan (Ca-SP) isolated from a blue-green alga, Spirulina platensis, which is a sulfated polysaccharide chelating calcium and mainly composed of rhamnose, on invasion of B16-BL6 melanoma, Colon 26 M3.1 carcinoma and HT-1080 fibrosarcoma cells through reconstituted basement membrane (Matrigel). Ca-SP significantly inhibited the invasion of these tumor cells through Matrigel/fibronectin-coated filters. Ca-SP also inhibited the haptotactic migration of tumor cells to laminin, but it had no effect on that to fibronectin. Ca-SP prevented the adhesion of B16-BL6 cells to Matrigel and laminin substrates but did not affect the adhesion to fibronectin. The pretreatment of tumor cells with Ca-SP inhibited the adhesion to laminin, while the pretreatment of laminin substrates did not. Ca-SP had no effect on the production and activation of type IV collagenase in gelatin zymography. In contrast, Ca-SP significantly inhibited degradation of heparan sulfate by purified heparanase. The experimental lung metastasis was significantly reduced by co-injection of B16-BL6 cells with Ca-SP. Seven intermittent i.v. injections of 100 microg of Ca-SP caused a marked decrease of lung tumor colonization of B16-BL6 cells in a spontaneous lung metastasis model. These results suggest that Ca-SP, a novel sulfated polysaccharide, could reduce the lung metastasis of B16-BL6 melanoma cells, by inhibiting the tumor invasion of basement membrane probably through the prevention of the adhesion and migration of tumor cells to laminin substrate and of the heparanase activity.

Anti-Invasive and Metastatic Activities of Evodiamine.

“…Evodiamine,13,13b,3Ј : 3,4] pyrido [2,1-b] quinazolin-5 one, was purchased from Matsuura Yakugyo Co., Ltd. Rutaecarpine, yohimbine, reserpine and indole were purchased from Wako Pure Chem. Ind., Ltd. 2-Mercapto-4(3H)-quinazolinone was purchased from Tokyo Kasei Kogyo Co., Ltd.…”

“…[3][4][5][6][7][8][9] We have recently reported that evodiamine can markedly inhibit in vitro invasion and lung metastasis by colon 26-L5 cells.…”

“…[3][4][5][6][7][8][9] We have recently reported that evodiamine can markedly inhibit in vitro invasion and lung metastasis by colon 26-L5 cells. 10) Evodiamine is one of the main constituents of Evodiae Fructus 11) and has been shown to possess anti-tumor growth, 12) anti-aldosterone releasing, 13) anti-obesity, 14) bronchoconstrictive, 15) anti-nociceptive, 16) vasorelaxant, 17) catecholamine-secretory 18) and anti-nitric oxide producing 19) properties.…”

Screening of Natural Compounds for Inhibitory Activity on Colon Cancer Cell Migration.

“…Most of these anti-metastatic activities are based on invasive inhibition by interfering with tumor adhesion to extracellular matrix components [4][5][6][7][8] or reducing tumor cell-associated protease activity. [9][10][11][12][13] Particularly, some matrix metalloproteinase inhibitors were recently applied to clinical trials.…”

Crude ethyl acetate extract of marine microalga,Chaetoceros calcitrans, induces Apoptosis in MDA-MB-231 breast cancer cells

“…[7,8] Spirulina is the most frequently studied marine algae. [9] In a previous study, notable antioxidant properties were found in both C. calcitrans and N. oculata . [10] The role of free radical scavenging in the prevention of cancer cell formation has been reported previously.…”