Glycotherapy for cancer: remodeling of ganglioside pattern as an effective approach for cancer therapy.
We have found that an increase in the ganglioside GM3 is a prerequisite for the induction of terminal differentiation, cuhninating in death by apoptosis, of human colonic carcinoma cells in vitro. To evaluate the therapeutic effect of increasing GM3 in human colonic carcinoma cells, we examined whether treated cells lose their tumorigenic activity and whether this approach is effective against cancer cells growing in vivo. Cells of the human colonic carcinoma cell line HCT 116 not only differentiated but also lost their tumorigenic activity by an artificial increase in GM3. When HCT 116 tumors growing in nude mice were treated with a drug that increases GM3, an appreciable increase in GM3 and induction of apoptosis were clearly observed. The growth of treated tumors was greatly suppressed. These results suggest that the modulation of ganglioside expression to introduce gangliosides with biological activity into cancer cells could be a novel effective approach for cancer therapy.
Nojiri
Hisao
H
Faculty of Pharmaceutical Sciences, Teikyo University, Tsukui-gun, Kanagawa, Japan. nojiri-h@pharm.teikyo-u.ac.jp
Yamana
Hideaki
H
Shirouzu
Genzan
G
Suzuki
Toshihide
T
Isono
Hideo
H
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020126:Brefeldin A / Q000627:therapeutic use*; D002454:Cell Differentiation; D002455:Cell Division; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005679:G(M3) Ganglioside / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005679:G(M3) Ganglioside; D020126:Brefeldin A