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金顶侧耳来源的葡糖醛酸木聚糖通过诱导细胞凋亡抑制 HT-29 人结肠癌细胞的体外和体内生长。

Glucuronorhamnoxylan from Capsosiphon fulvescens inhibits the growth of HT-29 human colon cancer cells in vitro and in vivo via induction of apoptotic cell death.

机构信息

Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do 14662, Republic of Korea.

Department of Marine Food Science and Technology, Gangneung-Wonju National University, 120 Gangneungdaehangno, Gangneung, Gangwon 25457, Republic of Korea.

出版信息

Int J Biol Macromol. 2019 Mar 1;124:1060-1068. doi: 10.1016/j.ijbiomac.2018.12.001. Epub 2018 Dec 3.

DOI:10.1016/j.ijbiomac.2018.12.001
PMID:30521889
Abstract

Colorectal cancer is the third most diagnosed cancer and a leading cause of cancer death. Dissatisfaction with currently available anti-colorectal cancer drugs caused by unwanted side effects and low efficacy necessitates new therapeutic agents. In the present study, a sulfated glucuronorhamnoxylan polysaccharide (named SPS-CF) purified from a green alga Capsosiphon fulvescens was evaluated for its anti-cancer activity in vitro and in vivo against colorectal cancer. The SPS-CF treatment resulted in a dose-dependent inhibition of the HT-29 human colon cancer cell growth up to 40% at 500 μg/mL. This inhibitory activity was shown to be mediated by upregulation of the cleavage of caspase-8, -9, -3 and poly (ADP-ribose) polymerase (PARP), induction of DNA fragmentation, and disruption of mitochondrial membrane potential (MMP), demonstrating that SPS-CF causes apoptotic death of HT-29 cancer cells though activation of caspase-dependant pathway. Administration of SPS-CF to BALB/c-nude mice bearing HT-29 cell-xenograft tumor also reduced the tumor growth. The results of this study demonstrated that the SPS-CF effectively inhibits the colorectal tumor growth both in vitro and in vivo by induction of apoptotic death of tumor cells, suggesting that it can be a potent ingredient for health-beneficial foods or anti-cancer agents to prevent or ameliorate human colon cancer.

摘要

结直肠癌是第三大常见癌症,也是癌症死亡的主要原因。由于存在不良反应和疗效低等问题,人们对现有的抗结直肠癌药物不满意,因此需要新的治疗药物。在本研究中,从一种绿藻 Capsosiphon fulvescens 中纯化得到的硫酸化葡糖醛酸鼠李半乳聚糖多糖(命名为 SPS-CF),对其在体外和体内抗结直肠癌的活性进行了评估。SPS-CF 处理导致 HT-29 人结肠癌细胞生长呈剂量依赖性抑制,在 500μg/mL 时高达 40%。这种抑制活性是通过上调半胱天冬酶-8、-9、-3 和多聚(ADP-核糖)聚合酶(PARP)的裂解、诱导 DNA 片段化以及破坏线粒体膜电位(MMP)来介导的,表明 SPS-CF 通过激活 caspase 依赖性途径导致 HT-29 癌细胞凋亡死亡。SPS-CF 给药给荷有 HT-29 细胞异种移植瘤的 BALB/c-裸鼠也减少了肿瘤生长。本研究结果表明,SPS-CF 通过诱导肿瘤细胞凋亡死亡,有效地抑制了体外和体内的结直肠肿瘤生长,提示它可以作为有益健康的食品或抗癌药物的有效成分,以预防或改善人类结肠癌。

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