A recombinant fungal compound induces anti-proliferative and pro-apoptotic effects on colon cancer cells

被引:17
|
作者
Nimri, Lili [1 ]
Spivak, Orly [1 ]
Tal, Dana [1 ]
Schaelling, Dominik [2 ]
Peri, Irena [1 ]
Graeve, Lutz [2 ]
Salame, Tomer M. [3 ]
Yarden, Oded [3 ]
Hadar, Yitzhak [3 ]
Schwartz, Betty [1 ]
机构
[1] Hebrew Univ Jerusalem, Inst Biochem Food Sci & Nutr, Robert H Smith Fac Agr Food & Environm, IL-76100 Rehovot, Israel
[2] Univ Hohenheim, Inst Biol Chem & Nutr, Fac Nat Sci, D-70599 Stuttgart, Germany
[3] Robert H Smith Fac Agr Food & Environm, Dept Plant Pathol & Microbiol, IL-76100 Rehovot, Israel
关键词
recombinant ostreolysin; colon cancer; pro-apoptotic; fungal; microtubule; MUSHROOM PLEUROTUS-OSTREATUS; PORE-FORMING PROTEIN; CYTOLYTIC PROTEIN; MEMBRANE CHOLESTEROL; COLORECTAL-CANCER; OYSTER MUSHROOM; OSTREOLYSIN; MECHANISMS; LYSOPHOSPHOLIPIDS; PLEUROTOLYSIN;
D O I
10.18632/oncotarget.15859
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Finding intracellular pathways and molecules that can prevent the proliferation of colon cancer cells can provide significant bases for developing treatments for this disease. Ostreolysin (Oly) is a protein found in the mushroom Pleurotus ostreatus, and we have produced a recombinant version of this protein (rOly). We measured the viability of several colon cancer cells treated with rOly. Xenografts and syngeneic colon cancer cells were injected into in vivo mouse models, which were then treated with this recombinant protein. rOly treatment induced a significant reduction in viability of human and mouse colon cancer cells. In contrast, there was no reduction in the viability of normal epithelial cells from the small intestine. In the search for cellular targets of rOly, we showed that it enhances the anti-proliferative activity of drugs targeting cellular tubulin. This was accompanied by a reduction in the weight and volume of tumours in mice injected with rOly as compared to their respective control mice in two in vivo models. Our results advance the functional understanding of rOly as a potential anticancer treatment associated with pro-apoptotic activities preferentially targeting colon cancer cells.
引用
收藏
页码:28854 / 28864
页数:11
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