Membrane resident peptide in anti-cancer peptides causes tumor cell necrosis rather than apoptosis of cancer cells
AssigneeThe Research Foundation of State University of New York
InventorsMatthew R. Pincus, Josef Michl, Ehsan Sarafraz-Yazdi
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Abstract
An aspect of the invention provides a method of selectively necrosing cells, comprising: providing a plurality cells, including at least one cancer cell and at least one non-cancerous cell; and administering to the cells a compound, including an HDM-2 targeting component and a cytotoxic component attached to the HDM-2 targeting component, wherein said compound comprises a membrane-active form.
Claims29
A method of selectively necrosing cells, comprising:
- providing a plurality cells, including at least one cancer cell and at least one non-cancerous cell;
- administering to the cells a compound, including an HDM-2 targeting component and a cytotoxic component, said cytotoxic component attached to said HDM-2 targeting component, wherein said compound comprises a membrane-active form.
A method of causing membranolysis in at least one cancer cell, comprising:
- administering to at least one cancer cell a compound comprising an HDM-2 targeting component and a pore-forming component attached to said HDM-2 targeting component, wherein said administering step results in at least one transmembrane pore in a cancer cell membrane.
A method of treating cancer in a subject in need thereof, comprising:
- administering to the subject in need thereof a therapeutically effective amount of a compound having an HDM-2 targeting component and a cytotoxic component, said HDM-2 targeting component and said cytotoxic component having a membrane-active form.
A method of screening cancer treatments, comprising:
- providing a plurality of cancerous cells;
- each of said cells having HDM-2 in said cellular membranes;
- administering a candidate cancer treatment to the plurality of cancer cells;
- and
- measuring the level of LDH present in a cellular medium.
A method of selectively necrosing cancer cells, comprising:
- providing a plurality of cells, including at least one cancer cell and at least one non-cancerous cell;
- and
- contacting the plurality of cells with an HDM-2 targeting compound which includes a membrane resident peptide (MRP), wherein the HDM-2 targeting compound colocalizes to HDM-2 present in at least one cancer cell membrane, binding to a cell membrane of the at least one cancer cell and adopting a membrane-resident conformation within said cancer cell membrane.
A method of identifying cancer cells, comprising:
- providing a plurality of cells, wherein at least one of said cells is a candidate cancer cell;
- and
- administering to the plurality of cells an HDM-2 recognition agent.
Dependencies are inferred from the claim text.