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

• Published in: Pharmaceutical biology Vol. 60; no. 1; pp. 909 - 914
• Main Authors: Zhai, Feng-guo, Liang, Qi-chao, Wu, Yi-yan, Liu, Jia-qi, Liu, Jia-wei
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01-12-2022; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Antitumor activity; Breast cancer; Breast Neoplasms - drug therapy; Cell proliferation; Cholecystokinin; Down-Regulation; Female; Ferroptosis; Ginseng; Humans; L-Lactate dehydrogenase; Lactic acid; Lung cancer; Medicinal plants; Panax; Panax ginseng; Polysaccharides; Polysaccharides - pharmacology; Reactive oxygen species; traditional Chinese medicine; breast cancer; traditional Chinese medicine; Lung cancer
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2022.2066139

Red ginseng polysaccharide (RGP) is an active component of the widely used medicinal plant Panax ginseng C. A. Meyer (Araliaceae), which has displayed promising activities against cancer cells. However, the detailed molecular mechanism of RGP in ferroptosis is still unknown.
This study evaluates the effects of RGP in cancer cells.
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.
RGP inhibited human A549 (IC
50
: 376.2 μg/mL) or MDA-MB-231(IC
50
: 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.
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.