Targeted Osmotic Lysis of Cancer Cells

Abstract

A targeted osmotic lysis (TOL) of tumor cells that over-express voltage-gated sodium channels (VGSCs) has been developed that uses a combined therapy of a drug that blocks sodium, potassium-adenosine triphosphatase (Na + , K + -ATPase) that is then followed by an activation of VGSCs, for example, by electrical or pharmacological stimulation. Activation of VGSCs conducts sodium into the cancer cells in much greater amounts than non-cancer cells. Water follows this sodium gradient into the cancer cells, causing swelling and lysis. Because non-cancerous cells do not over-express VGSCs, less sodium and less water will enter the cells, and the non-cancerous cells will not lyse. This method is applicable to all cells that over-express VGSCs, including, but not limited to, highly invasive breast cancer, prostate cancer, small cell lung cancer, non-small cell lung carcinoma, lymphoma, mesothelioma, neuroblastoma, and cervical cancer.

What is claimed: 
     
         1 . A method for treating cancer in a mammal; wherein, as compared to normal cells, cells of the cancer over-express voltage-gated sodium channels; said method comprising co-administering to the cancerous cells a first agent and a second agent; wherein:
 (a) the first agent comprises a drug compound that decreases the activity or expression of sodium, potassium-adenosine triphosphatase;   (b) the second agent stimulates the activity of voltage-gated sodium channels;   (c) the combined effects of the first agent on sodium, potassium-adenosine triphosphatase and of the second agent on voltage-gated sodium channels induce, within one day of said co-administration, the osmotic lysis of cancerous cells that over-express voltage-gated sodium channels; and   (d) non-cancerous muscle cells, non-cancerous peripheral nerve cells, non-cancerous heart cells, and non-cancerous brain cells are not osmotically lysed following said co-administration.   
     
     
         2 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         3 . The method of  claim 1 , wherein the cancer is selected from the group consisting of breast cancer, prostate cancer, small cell lung cancer, non-small cell lung carcinoma, lymphoma, mesothelioma, neuroblastoma, glioma, neuroma, hepatic cancer, ovarian cancer, bladder cancer, pancreatic cancer, thyroid cancer, splenic cancer, stomach cancer, skin cancer, testicular cancer, renal cancer, oral cancer, and cervical cancer. 
     
     
         4 . The method of  claim 1 , wherein the cancer is breast cancer. 
     
     
         5 . The method of  claim 1 , wherein the cancer is prostate cancer. 
     
     
         6 . The method of  claim 1 , wherein the cancer is colon cancer. 
     
     
         7 . The method of  claim 1 , wherein the cancer is small cell lung cancer. 
     
     
         8 . The method of  claim 1 , wherein the cancer is non-small cell lung cancer. 
     
     
         9 . The method of  claim 1 , wherein the first agent comprises one or more drug compounds selected from the group consisting of digoxin, digitoxin, digitalis, ouabain, oleandrin, dihydroouabain, ouabain octahydrate, ouabagenin, acetyldigitoxin, acetyldigoxin, lanatoside C, deslanoside, metildigoxin, gitoformate, oleandrigenin, bufotoxin, bufotalin, marinobufagenin, palytoxin; oligomycins, rutamycin, rutamycin B, strophanthin, k-β-strophanthin, strophanthidin, k-strophanthoside, cymarin, erysimoside (cardenolide), helveticoside, peruvoside, hypothalamic sodium, potassium-adenosine triphosphatase inhibitory factor (HIF), the aglycone of HIF, arenobufagin, cinobufagin, marinobufagin, proscillaridin, scilliroside, and daigremontianin. 
     
     
         10 . The method of  claim 1 , wherein the first agent comprises ouabain. 
     
     
         11 . The method of  claim 1 , wherein the first agent comprises digitoxin. 
     
     
         12 . The method of  claim 1 , wherein the second agent comprises a drug that stimulates the activity of voltage-gated sodium channels. 
     
     
         13 . The method of  claim 1 , wherein the second agent comprises one or more drug compounds selected from the group consisting of veratridine, veracevine, antillatoxin (ATX), ATX II, batrachotoxin, aconitine, grayanotox, Grayanotoxin III Hemi(ethyl acetate), Antillatoxinn, Nigericin, gramicidin, α-Pompilidotoxin, β-Pompilidotoxin, Hoiamide A, brevetoxin (PbTx-2), ciguatoxins, scorpion neurotoxin, Cypermethrin, Alphamethrin, and palytoxin. 
     
     
         14 . The method of  claim 1 , wherein the second agent drug comprises veratridine. 
     
     
         15 . The method of  claim 1 , wherein the second agent comprises an electrical current. 
     
     
         16 . The method of  claim 1 , wherein the second agent comprises ultrasound. 
     
     
         17 . The method of  claim 1 , wherein the second agent comprises a magnetic field.