Various physiological benefits have been linked to Hizikia fusiforme (HF), an edible brown\nseaweed. Here, fucose-containing sulfated polysaccharides were extracted from celluclast-processed\nHF (SPHF) and their antitumor effcacy against bladder cancer was evaluated in vitro and in vivo.\nSPHF possesses high sulfated polysaccharide and fucose contents and free radical scavenging activities\ncompared to those of celluclast-processed HF extracts (CHF). SPHF inhibited bladder cancer EJ cell\nproliferation via G1-phase cell cycle arrest. This was due to the induction of p21WAF1 expression\nassociated with the downregulation of CDKs and cyclins. Moreover, JNK phosphorylation was\nidentified as an SPHF-mediated signaling molecule. SPHF treatment also hindered the migration\nand invasion of EJ cells by inhibiting MMP-9 expression, which was attributed to the repression of\ntranscriptional binding to NF-B, AP-1, and Sp-1 in the MMP-9 promoter region. In an animal study,\nSPHF treatment suppressed EJ tumor growth in xenograft mice similarly to cisplatin. Furthermore,\nno toxicity signs were found after weight loss assessment, biochemical tests, and organ tissue\nimmunostaining during oral administration of 20â??200 mg/kg SPHF for 20 days. Therefore, our study\ndemonstrates the antitumor effcacy of SPHF in vitro and in vivo, thus highlighting its potential for\nbladder cancer treatment development.
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