Published in Cancer Detection and Prevention 2002; 26(2).

Glycotherapy for cancer: remodeling of ganglioside pattern as an effective approach for cancer therapy

Hisao Nojiri, PhD a, Hideaki Yamana, MD b, Genzan Shirouzu, MD b, Toshihide Suzuki, PhD a, Hideo Isono, PhD a.

a Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko-machi, Tsukui-gun. 199-0195 Kanagawa, Japan b Deparmtent of Surgery, School of Medicine, Kurume University, Fukuoka, Japan

accepted 1 March 2002

We have found that an increase in the ganglioside GM3 is a prerequisite for the induction of tenninal differentiation, culminating 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.

KEY WORDS: Ganglioside, Differentiation, Apoptosis, Human colonic carcinoma cell, Brefeldin A.