Evaluation of sulfated α-glucans from Poria cocos mycelia as potential antitumor agent

Six water-soluble sulfated derivatives (S1-S6) having molecular mass (M-W) from 2.65 X 10(4) to 14.5 X 10(4) were synthesized from the corresponding fractions of water-insoluble (1 -> 3)-alpha-D-glucan (Pi-PCM3-I) isolated from pilot-scale product of Poria cocos mycelia. All sulfated derivatives had markedly higher antitumor activities in vivo (Sarcoma 180 solid tumor inoculated on BALB/c mice) as well as in vitro against human hepatoma cell HepG2 and S-180 tumor cell compared with the native non-sulfated (1 -> 3)-alpha-D-glucan, and showed much lower toxicity than 5-Fu. Interestingly, the sulfated derivatives having moderate M, exhibited more pronounced inhibition ratio, indicating the effect of M, on bioactivities for the sulfated alpha-glucans. Using the fluorescence microscopy with Propidium iodide (PI)/Hoechst33342 staining, the mechanism involved in sulfated alpha-glucan-induced HepG2 cell apoptosis and necrosis was assessed morphologically. The results revealed that the sulfated derivative induced time-dependent increases in apoptosis (p < 0.05). In view of immunohistochemical assays, the sulfated derivative can accelerate apoptosis in S-180 tumor cell by up-regulation of Bax (pro-apoptosis) and down-regulation of Bcl-2 (anti-apoptosis). A low Bcl-2:Bax ratio (0.27,p < 0.05) caused by high Bax expression (50.3%,p < 0.05) with low Bcl-2 (13.7%,p < 0.05) indicated that the sulfated derivative had good therapeutic effect on tumor cell and the potential of clinical application as a cherntherapeutic agent. (c) 2005 Elsevier Ltd. All rights reserved.