Lentinan inhibited colon cancer growth by inducing endoplasmic reticulum stress-mediated autophagic cell death and apoptosis. (1st September 2021)

• Record Type: Journal Article
• Authors: Zhang, Yu; Liu, Yan; Zhou, Yinxing; Zheng, Ziming; Tang, Wenqi; Song, Mengzi; Wang, Jinglin; Wang, Kaiping
• Is Part Of: Carbohydrate polymers. Volume 267(2021)
• Publication Date: 2021-09-01
• Subjects: SLNT lentinan -- ERS endoplasmic reticulum stress -- NOD/SCID nonobese diabetic/severe combined immunodeficiency -- CQ chloroquine -- 3-MA 3-methyladenine -- 4-PBA sodium 4-phenylbutyrate -- 2-APB 2-aminoethoxydiphenyl borate -- DBSA 3, 5-dibromosalicyladehyde -- PERK PKR-like kinase -- IRE1α inositol- requiring enzyme 1α -- eIF2α eukaryotic translation initiation factor 2α -- ATF4 activating transcription factor 4 -- BIP/GRP78 78-kDa glucose-regulated protein -- CHOP C/EBP homologous protein -- LC3 microtubule-associated protein 1A/1B-light chain 3 -- IP3R inositol-1, 4, 5-triphosphate receptor -- JNK c-Jun N-terminal kinase; Lentinan -- Direct antitumour -- NOD/SCID mice -- Endoplasmic reticulum stress -- Autophagy -- Apoptosis; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2021.118154
• Languages: English
• ISSNs: 0144-8617

Abstract

Abstract: Lentinan (SLNT) has been shown to be directly cytotoxic to cancer cells. However, this direct antitumour effect has not been thoroughly investigated in vivo, and the mechanism remains unclear. We aimed to examine the direct antitumour effect of SLNT on human colon cancer and the mechanism in vivo and in vitro . SLNT significantly inhibited tumour growth and induced autophagy and endoplasmic reticulum stress (ERS) in HT-29 cells and tumour-bearing nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. Experiments with the autophagy inhibitors chloroquine (CQ) and 3-methyladenine (3-MA) showed that autophagy facilitated the antitumour effect of SLNT. Moreover, ERS was identified as the common upstream regulator of SLNT-induced increases in Ca 2+ concentrations, autophagy and apoptosis by using ERS inhibitors. In summary, our study demonstrated that SLNT exerted direct antitumour effects on human colon cancer via ERS-mediated autophagy and apoptosis, providing a novel understanding of SLNT as an anti-colon cancer therapy. Highlights: Lentinan (SLNT) inhibited HT-29 xenograft tumour growth in NOD/ SCID mice. SLNT induced autophagic cell death and endoplasmic reticulum stress (ERS) in vivo and in vitro . SLNT-induced ERS is the common upstream regulator of autophagy and apoptosis.