Methods and compositions for promoting activity of anti-cancer therapies

Abstract

The present invention relates to a method of inhibiting growth of a cancerous cell. The method includes the step of exposing the cancerous cell to an anti-cancer therapy and an effective amount of a steroid saponin.

1 . A method of inhibiting growth of a cancerous cell, the method including the step of exposing the cancerous cell to an anti-cancer therapy and an effective amount of a steroid saponin. 
   
   
       2 . A method according to  claim 1 , wherein the steroid saponin includes a saccharide attached to a single position of the sapogenin component of the steroid saponin. 
   
   
       3 . A method according to  claim 2 , wherein the saccharide is attached to the C-3 position of the sapogenin. 
   
   
       4 . A method according to  claim 2 , wherein the saccharide includes one or more monosaccharide units selected from D-glucose (Glc), L-rhamnose (Rha), D-galactose (Gal), D-glucuronic acid (GlcA), D-xylose (Xyl), L-arabinose (Ara), D-fucose (Fuc), D-galacturonic acid (GalA). 
   
   
       5 . A method according to  claim 1 , wherein the sapogenin component of the steroid saponin is based on a sapogenin selected from the group consisting of a spirostanol, including diosgenin, yamogenin (neodiosgenin), yuccagenin, sarsasapogenin, tigogenin, smilagenin, hecogenin, gitogenin, convallamarogenin, neoruscogenin, and solagenin; a furostanol including protodiosgenin, pseudoprotodiosgenin, methyl protodiosgenin, protoyamogenin and methyl protoyamogenin. 
   
   
       6 . A method according to  claim 1 , wherein the steroid saponin is a chacotrioside-steroid saponin or a solatrioside-steroid saponin. 
   
   
       7 . (canceled) 
   
   
       8 . A method according to  claim 6 , wherein the chacotrioside-steroid saponin is selected from the group consisting of diosgenin linked through the C-3 position to chacotriose; diosgenin linked through the C-3 position to another chacotrioside; tigogenin linked through the C-3 position to a chacotrioside; sarsasapogenin linked through the C-3 position to a chacotrioside; smilagenin linked through the C-3 position to a chacotrioside; yuccagenin linked through the C-3 position to a chacotrioside; and yamogenin linked through the C-3 position to a chacotrioside, and wherein the solatrioside-steroid saponin is selected from the group consisting of gracillin; deltonin; diosgenin solatriose; diosgenin linked through the C-3 position to another solatrioside; tigogenin linked through the C-3 position to a solatrioside; sarsasapogenin linked through the C-3 position to a solatrioside; smilagenin linked through the C-3 position to a solatrioside; yuccagenin linked through the C-3 position to a solatrioside; and yamogenin linked through the C-3 position to a solatrioside. 
   
   
       9 . (canceled) 
   
   
       10 . A method according to  claim 1 , wherein the steroid saponin has the chemical formula: 
     
       
         
         
             
             
         
       
     
     wherein
 R1, R2, R4, R6, R7, R11, R12, R14, R15 and R17 are independently H, OH, ═O, pharmacologically acceptable ester groups or pharmacologically acceptable ether groups; 
 R5 is H when C-5,C-6 is a single bond, and nothing when C-5,C-6 is a double bond; 
 A is either O concurrently with B being CH 2 , or B is O concurrently with A being CH 2 ; 
 R27A is H concurrently with R27B being CH3, or R27A is CH3 concurrently with R27B being H; 
 R3 comprises a glycosyl group linked through the oxygen atom to the steroidal sapogenin at C-3; 
 
     or a pharmaceutically acceptable salt, or derivative thereof. 
   
   
       11 . A method according to  claim 1 , wherein the steroid saponin has the chemical formula: 
     
       
         
         
             
             
         
       
     
     wherein
 R1, R2, R4, R6, R7, R11, R12, R14, R15 and R17 are independently H, OH, ═O, pharmacologically acceptable ester groups or pharmacologically acceptable ether groups; 
 R5 is H when C-5,C-6 is a single bond, and nothing when C-5,C-6 is a double bond; 
 R22 is either a hydroxyl or an alkoxyl group when C-20, C-22 is a single bond, or nothing when C-20, C-22 is a double bond; 
 R 27A  is H concurrently with R 27B  being CH 3 , or R 27A  is CH 3  concurrently with R 27B  being H; 
 R28 is H or a saccharide; or a pharmaceutically acceptable salt, or derivative thereof; 
 R3 comprises a glycosyl group linked through the oxygen atom to the steroidal sapogenin at C-3; 
 
     or a pharmaceutically acceptable salt, or derivative thereof. 
   
   
       12 . A method according to  claim 1 , wherein the steroid saponin is selected from the group consisting of diosgenin linked through the C-3 position to a saccharide, tigogenin linked through the C-3 position to a saccharide, sarsasapogenin linked through the C-3 position to a saccharide, smilagenin linked through the C-3 position to a saccharide, yuccagenin linked through the C-3 position to a saccharide, and yamogenin linked through the C-3 position to a saccharide. 
   
   
       13 .- 17 . (canceled) 
   
   
       18 . A method according to  claim 1 , wherein the steroid saponin is selected from the group consisting of deltonin (diosgenin Rha2, [Glc4], Glc), dioscin (diosgenin Rha2, [Rha4], Glc), prosapogenin A (diosgenin Rha2, Glc) and asperin (diosgenin [Rha 4, Rha 4], Rha 2, Glc). 
   
   
       19 . A method according to  claim 1 , wherein the anti-cancer therapy is exposure of the cell to an anti-cancer agent, or is radiotherapy. 
   
   
       20 . (canceled) 
   
   
       21 . A method according to  claim 19 , wherein the anti-cancer agent is an agent selected from one or more of the group consisting of alkylating agents, including BCNU (carmustine), bisulfan, CCNU (lomustine), chlorambucil, cisplatin, melphan, mitomycin C, and thio-tepa; antimitotic agents including taxol (paclitaxel), docetaxel, vinblastine sulphate, and vincristine sulphate; topoisomerase inhibitors including doxorubicin, daunorubicin, m-AMSA (amsacrine), mitoxantrone, and VP-16 (etoposide); RNA/DNA antimetabolites including 5-fluorouracil and methotrexate; DNA antimetabolites including Ara-C (cytarabine), hydroxyurea (hydroxycarbamide), and thioguanine (tioguanine); a cellular process targeting agent; imatinib mesylate; trastuzumab; and gefitinib. 
   
   
       22 .- 29 . (canceled) 
   
   
       30 . A method of promoting the activity of an anti-cancer therapy in a subject, the method including exposing the subject to an effective amount of a steroid saponin. 
   
   
       31 .- 43 . (canceled) 
   
   
       44 . A method of promoting apoptosis of a cancerous cell due to exposure of the cancerous cell to an anti-cancer therapy, the method including exposing the cancerous cell to an effective amount of a steroid saponin. 
   
   
       45 .- 54 . (canceled) 
   
   
       55 . A method according to  claim 1 , wherein the method is used to inhibit formation and/or growth of a tumor in a subject. 
   
   
       56 . A method according to  claim 1 , wherein the method is used to prevent and/or treat cancer in a subject. 
   
   
       57 . A method according to  claim 30 , wherein the method is used to reduce the amount of the anti-cancer therapy provided to the subject to prevent and/or treat a cancer in the subject. 
   
   
       58 . A method according to  claim 30 , wherein the method is used to prevent and/or treat a cancer in the subject, wherein the subject has an increased resistance to the anti-cancer therapy. 
   
   
       59 . A method according to  claim 44 , wherein the method reduces resistance developing to the anti-cancer therapy in the cancerous cell.