College of Chemistry and Molecular Sciences, Hubei Engineering Center of Natural Polymer-Based Medical Materials, Wuhan University, Wuhan 430072, China.
Department of Radiation and Medical Oncology, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Int J Biol Macromol. 2023 Nov 1;251:126222. doi: 10.1016/j.ijbiomac.2023.126222. Epub 2023 Aug 15.
This study demonstrates that the purified β-glucan (LNT) with a triple helix and relatively narrow molecular weight distribution, extracted and purified from artificially cultured Lentinus edodes, showed a significant cervical cancer inhibition with little cytotoxicity against normal cells in vitro and in vivo. From the in vitro data, the potential mechanism of anti-cervical cancer was preliminarily revealed as follows: LNT was firstly recognized by the human cervical cancer cell line of Hela and induced cell proliferation inhibition through p21 and apoptosis via a mitochondrion-dependent pathway by targeting the tumor suppressor of p53, indicated by an increase in reactive oxygen species (ROS) generation and a loss of mitochondrial membrane potential (Δψ), in a significant dosage-dependent manner. Meanwhile, LNT repressed tumor growth with an inhibition ratio of 61.2 % and induced tumor cell apoptosis through endogenous MDM2/p53/Bax/mitochondrion signal pathway by up-regulating the expression of p53, Bax, Cyt. c, caspase 9, and caspase 3, as well as down-regulating Bcl-2, MDM2, and PARP1 levels in Hela cells-transplanted BALB/c nude mice. This study provides a scientific basis for the clinical treatment of cervical cancer with LNT as a potential drug candidate characterized by the triple helix and specified molecular weight with a relatively narrow distribution.
本研究表明，从人工栽培香菇中提取和纯化的具有三重螺旋结构且分子量分布较窄的β-葡聚糖（LNT），在体外和体内对正常细胞几乎没有细胞毒性，但对宫颈癌具有显著抑制作用。从体外数据初步揭示了其抗癌的潜在机制：LNT 首先被人宫颈癌 Hela 细胞系识别，并通过靶向肿瘤抑制因子 p53，通过线粒体依赖性途径诱导细胞增殖抑制和凋亡，表现为活性氧（ROS）生成增加和线粒体膜电位（Δψ）丧失，呈显著剂量依赖性。同时，LNT 通过上调 p53、Bax、Cyt.c、caspase 9 和 caspase 3 的表达，下调 Bcl-2、MDM2 和 PARP1 水平，抑制肿瘤生长，抑制率为 61.2%，并通过内源性 MDM2/p53/Bax/线粒体信号通路诱导肿瘤细胞凋亡，在荷瘤 BALB/c 裸鼠体内。该研究为 LNT 作为一种具有三重螺旋结构和特定分子量分布较窄的潜在药物候选物治疗宫颈癌提供了科学依据。
