In Vitro and In Vivo Antitumor Efficacy of Hizikia fusiforme Celluclast Extract against Bladder Cancer

Abstract

Various physiological benefits have been linked to Hizikia fusiforme (HF), an edible brown seaweed. Here, fucose-containing sulfated polysaccharides were extracted from celluclast-processed HF (SPHF) and their antitumor efficacy against bladder cancer was evaluated in vitro and in vivo. SPHF possesses high sulfated polysaccharide and fucose contents and free radical scavenging activities compared to those of celluclast-processed HF extracts (CHF). SPHF inhibited bladder cancer EJ cell proliferation via G1-phase cell cycle arrest. This was due to the induction of p21WAF1 expression associated with the downregulation of CDKs and cyclins. Moreover, JNK phosphorylation was identified as an SPHF-mediated signaling molecule. SPHF treatment also hindered the migration and invasion of EJ cells by inhibiting MMP-9 expression, which was attributed to the repression of transcriptional binding to NF-κB, AP-1, and Sp-1 in the MMP-9 promoter region. In an animal study, SPHF treatment suppressed EJ tumor growth in xenograft mice similarly to cisplatin. Furthermore, no toxicity signs were found after weight loss assessment, biochemical tests, and organ tissue immunostaining during oral administration of 20–200 mg/kg SPHF for 20 days. Therefore, our study demonstrates the antitumor efficacy of SPHF in vitro and in vivo, thus highlighting its potential for bladder cancer treatment development.

Bioactivities of the Popular Edible Brown Seaweed Sargassum fusiforme: A Review

“…In addition, SPHF inhibited migration and invasion of EJ cells by reduction of the transcription factor related matrix metalloprotein (MMP-9) expression. 102 Fan et al studied the antitumor effect of S. f usiforme polysaccharide on nasopharyngeal carcinoma (NPC) and its potential mechanism on spleen lymphocytes. The outcome showed that the polysaccharides remarkably suppressed the growth of human nasopharyngeal cancer cells (CNEs) in vitro and improved the levels of serum cytokines and immunoglobulin M (IgM) in mice.…”

“…Many reports indicate that the active substances in S. fusiforme have antitumor effects. ,− Kim et al isolated saringosterol acetate (SSA) from S. fusiforme and established the effect of SSA on tumor growth and metastasis in an adult zebrafish human hepatocellular carcinoma (HCC) xenotransplantation model . The results showed that SSA affects survival rate, alpha-fetoprotein (AFP) production, the level of the factors related to tumor growth and metastasis via regulating phosphoinositide 3-kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) and transforming growth factor-beta (TGF-β)/Smad pathways .…”

“…SPHF inhibits p21WAF1 by inducing the expression of cyclin-dependent kinases (CDK) and cell cycle related proteins, thereby mediating the G1 phase cell cycle to prevent the proliferation of bladder cancer (EJ) cells. In addition, SPHF inhibited migration and invasion of EJ cells by reduction of the transcription factor related matrix metalloprotein (MMP-9) expression . Fan et al studied the antitumor effect of S. fusiforme polysaccharide on nasopharyngeal carcinoma (NPC) and its potential mechanism on spleen lymphocytes.…”

Seaweed Exhibits Therapeutic Properties against Chronic Diseases: An Overview

“…In vitro Inhibited the growth of U87MG cell line [129] Carrageenan extract from Gigartina pistillata inhibits cell growth in colorectal cancer stem cells with an IC 50 value of 1 µg/mL [125]. Moreover, Hizikia fusiforme inhibited EJ tumor growth both in vivo and in vitro through G1-phase cell cycle arrest by downregulating cyclins and cyclin-dependent kinases (CDKs), as well as by inhibiting the expression of MMP-9 by downregulating NF-κB, AP-1, and Sp-1 [122]. In addition, seaweed extract also exhibited potent anticancer activity against hepatocellular carcinoma (HCC) cell lines [123], the U87MG cell line [129], and sarcoma 180 ascites tumor cells both in vitro and in vivo [126].…”