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红参多糖通过下调 GPX4 诱导铁死亡发挥抗癌活性。

Red ginseng polysaccharide exhibits anticancer activity through GPX4 downregulation-induced ferroptosis.

机构信息

Department of Pharmacology, Mudanjiang Medical University, Mudanjiang, China.

出版信息

Pharm Biol. 2022 Dec;60(1):909-914. doi: 10.1080/13880209.2022.2066139.

DOI:10.1080/13880209.2022.2066139
PMID:35575436
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9116236/
Abstract

CONTEXT

Red ginseng polysaccharide (RGP) is an active component of the widely used medicinal plant C. A. Meyer (Araliaceae), which has displayed promising activities against cancer cells. However, the detailed molecular mechanism of RGP in ferroptosis is still unknown.

OBJECTIVE

This study evaluates the effects of RGP in cancer cells.

MATERIALS AND METHODS

A549 and MDA-MB-231 cells were used. Cell proliferation was measured by CCK-8 assay after being treated with RGP at concentrations of 0, 50, 100, 200, 400, 800 and 1600 μg/mL at 0, 12, 24 and 48 h. Lipid reactive oxygen species (ROS) levels were assessed by C11-BODIPY assay. The control group was treated with PBS.

RESULTS

RGP inhibited human A549 (IC: 376.2 μg/mL) or MDA-MB-231(IC: 311.3 μg/mL) proliferation and induced lactate dehydrogenase (LDH) release, promoted ferroptosis and suppressed the expression of GPX4. Moreover, the effects of RGP were enhanced by the ferroptosis inducer erastin, while abolished by ferroptosis inhibitor ferrostatin-1.

DISCUSSION AND CONCLUSIONS

Our study is the first to demonstrate (1) the anticancer activity of RGP in human lung cancer and breast cancer. (2) RGP presented the anti-ferroptosis effects in lung and breast cancer cells via targeting GPX4.

摘要

背景

红参多糖(RGP)是广泛应用的药用植物 C. A. Meyer(伞形科)的一种活性成分,它对癌细胞表现出有希望的活性。然而,RGP 在铁死亡中的详细分子机制尚不清楚。

目的

本研究评估 RGP 在癌细胞中的作用。

材料和方法

使用 A549 和 MDA-MB-231 细胞。用浓度为 0、50、100、200、400、800 和 1600μg/mL 的 RGP 在 0、12、24 和 48h 处理后,通过 CCK-8 测定法测量细胞增殖。通过 C11-BODIPY 测定法评估脂质活性氧(ROS)水平。对照组用 PBS 处理。

结果

RGP 抑制人 A549(IC:376.2μg/mL)或 MDA-MB-231(IC:311.3μg/mL)增殖并诱导乳酸脱氢酶(LDH)释放,促进铁死亡并抑制 GPX4 的表达。此外,铁死亡诱导剂 erastin 增强了 RGP 的作用,而铁死亡抑制剂 ferrostatin-1 则消除了其作用。

讨论和结论

我们的研究首次证明了:(1)RGP 在人肺癌和乳腺癌中的抗癌活性。(2)RGP 通过靶向 GPX4 在肺癌和乳腺癌细胞中呈现抗铁死亡作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0261/9116236/6c141f1518b9/IPHB_A_2066139_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0261/9116236/398486d21932/IPHB_A_2066139_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0261/9116236/bb3779baafa4/IPHB_A_2066139_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0261/9116236/af18909cc4ac/IPHB_A_2066139_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0261/9116236/6c141f1518b9/IPHB_A_2066139_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0261/9116236/398486d21932/IPHB_A_2066139_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0261/9116236/bb3779baafa4/IPHB_A_2066139_F0002_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0261/9116236/af18909cc4ac/IPHB_A_2066139_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0261/9116236/6c141f1518b9/IPHB_A_2066139_F0004_C.jpg

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