A novel anticancer property of Lycium barbarum polysaccharide in triggering ferroptosis of breast cancer cells
A novel anticancer property of Lycium barbarum polysaccharide in triggering ferroptosis of breast cancer cells
复制标题
枸杞多糖诱导乳腺癌细胞铁凋亡的抗癌新特性
DOI：
10.1631/jzus.b2100748
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发表时间：
2022-04-01
影响因子：
5.1
通讯作者：
Hou, Shaozhang
中科院分区：
文献类型：
--
作者：
Du, Xing;Zhang, Jingjing;Hou, Shaozhang
乳腺癌是最恶性的肿瘤之一，与妇女的高死亡率有关。枸杞多糖（Lycium barbarum polysaccharide，LBP）是从传统中草药枸杞（Lycium barbarum）果实中提取的一种多糖。枸杞枸杞多糖具有高效、低毒的特点，是一种很有前途的抗肿瘤药物。虽然它具有抗癌特性，但其作用机制尚未完全确定。铁凋亡是一种新的抗癌策略，是一种依赖于铁依赖性脂质活性氧（ROS）积累的细胞死亡机制。在这项研究中，人乳腺癌细胞（密歇根癌症基金会-7（MCF-7）和MD安德森转移性乳腺癌-231（MDA-MB-231））用LBP处理。LBP抑制其活力和增殖与高水平的铁凋亡。因此，我们旨在确定LBP是否通过铁凋亡降低细胞活力。我们发现LBP改变了线粒体的结构和功能、脂质过氧化以及溶质载体家族7成员11（SLC 7A 11，也称为xCT，胱氨酸/谷氨酸反向转运体系统X-c（-）的轻链亚基）和谷胱甘肽过氧化物酶4（GPX 4）的表达。此外，铁凋亡抑制剂，Ferrostatin-1（Fer-1），挽救了LBP诱导的铁凋亡相关事件，包括降低细胞活力和谷胱甘肽（GSH）的生产，细胞内游离二价铁离子和丙二醛（MDA）的积累，以及xCT和GPX 4的表达下调。Erastin（xCT抑制剂）和RSL 3（GPX 4抑制剂）分别抑制xCT和GPX 4的表达，在LBP与Erastin和RSL 3共同处理后，xCT和GPX 4的表达降低。这些结果表明，LBP有效地防止乳腺癌细胞增殖，并通过xCT/GPX 4途径促进铁凋亡。因此，LBP通过触发铁凋亡而表现出新的抗癌特性，并且可能是乳腺癌的潜在治疗选择。
Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women. Lycium barbarum polysaccharide (LBP) is an extract from the fruits of the traditional Chinese herb, L. barbarum. LBP is a promising anticancer drug, due to its high activity and low toxicity. Although it has anticancer properties, its mechanisms of action have not been fully established. Ferroptosis, which is a novel anticancer strategy, is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species (ROS) accumulation. In this study, human breast cancer cells (Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-Metastatic Breast-231 (MDA-MB-231)) were treated with LBP. LBP inhibited their viability and proliferation in association with high levels of ferroptosis. Therefore, we aimed to ascertain whether LBP reduced cell viability through ferroptosis. We found that the structure and function of mitochondria, lipid peroxidation, and expression of solute carrier family 7 member 11 (SLC7A11, also known as xCT, the light-chain subunit of cystine/glutamate antiporter system X-c(-)) and glutathione peroxidase 4 (GPX4) were altered by LBP. Moreover, the ferroptosis inhibitor, Ferrostatin-1 (Fer-1), rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione (GSH) production, accumulation of intracellular free divalent iron ions and malondialdehyde (MDA), and down-regulation of the expression of xCT and GPX4. Erastin (xCT inhibitor) and RSL3 (GPX4 inhibitor) inhibited the expression of xCT and GPX4, respectively, which was lower after the co-treatment of LBP with Erastin and RSL3. These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the xCT/GPX4 pathway. Therefore, LBP exhibits novel anticancer properties by triggering ferroptosis, and may be a potential therapeutic option for breast cancer.