A Small Molecular Weight Saccharide Fraction From Panax quinquefolium L. Inhibited Non‐Small Cell Lung Cancer via Endoplasmic Reticulum‐Stress Mediated Apoptosis
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Wiley
2025
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| author | Jia‐Lu Lü Jun Liang Yi Zhang Xue‐Qing Liu Wen‐Fei Wang Hai‐Xue Kuang Yong‐Gang Xia |
| author_facet | Jia‐Lu Lü Jun Liang Yi Zhang Xue‐Qing Liu Wen‐Fei Wang Hai‐Xue Kuang Yong‐Gang Xia Jia‐Lu Lü Jun Liang Yi Zhang Xue‐Qing Liu Wen‐Fei Wang Hai‐Xue Kuang Yong‐Gang Xia |
| collection | Wiley Open Access |
| contents | A Small Molecular Weight Saccharide Fraction From Panax quinquefolium L. Inhibited Non‐Small Cell Lung Cancer via Endoplasmic Reticulum‐Stress Mediated Apoptosis Jia‐Lu Lü Jun Liang Yi Zhang Xue‐Qing Liu Wen‐Fei Wang Hai‐Xue Kuang Yong‐Gang Xia Phytotherapy Research ABSTRACTNon‐small cell lung cancer remains a significant global health challenge. The limited efficacy, drug resistance, and toxicity of current treatments highlight the need for novel therapeutics. While Panax quinquefolium L. has demonstrated anti‐tumor activity in previous studies, the therapeutic potential of its small molecular weight saccharide fraction (SFPQ) remains unexplored. This study investigates the anti‐tumor efficacy and mechanisms of SFPQ, aiming to establish its potential as a novel anti‐cancer agent. SFPQ was isolated via macroporous resin adsorption and ultrafiltration, then characterized by LC–MS/MS analysis. In vitro cytotoxicity was assessed using CCK‐8 and colony formation assays, and apoptosis was quantified via flow cytometry. Live‐cell fluorescent labeling and confocal microscopy confirmed the specificity of SFPQ for the endoplasmic reticulum. Mechanistic insights into endoplasmic reticulum stress were elucidated via bioinformatics analysis, Western blot, and RT‐qPCR assays. Lentiviral transduction and pharmacological inhibition validated SFPQ‐mediated regulation of IRE1/JNK phosphorylation and c‐Myc expression. In vivo anti‐tumor efficacy and safety were assessed using xenograft models, complemented by morphometric parameters analysis and histopathology. CCK‐8 and colony formation assay demonstrated cytotoxic effects of SFPQ on non‐small cell lung cancer cells. SFPQ significantly promoted endoplasmic reticulum Ca2+ efflux, altered endoplasmic reticulum morphology, and increased the apoptosis rate for A549 cells. Live‐cell imaging confirmed strong endoplasmic reticulum affinity, while mechanistic studies demonstrated that SFPQ triggered endoplasmic reticulum stress‐mediated apoptosis via the IRE1/JNK/c‐Myc axis. In xenograft models, SFPQ significantly reduced tumor volume and weight in a dose‐dependent manner, showing comparable efficacy to cisplatin. Histopathological analysis further confirmed SFPQ's favorable safety profile. This study elucidates the endoplasmic reticulum stress‐mediated anti‐lung cancer mechanism of SFPQ through IRE1/JNK/c‐Myc signaling. SFPQ exhibits potent anti‐lung cancer activity in vitro and in vivo with minimal systemic toxicity, supporting its potential as a novel therapeutic agent. 10.1002/ptr.70036 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/ptr.70036 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_ptr_70036 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | A Small Molecular Weight Saccharide Fraction From Panax quinquefolium L. Inhibited Non‐Small Cell Lung Cancer via Endoplasmic Reticulum‐Stress Mediated Apoptosis Jia‐Lu Lü Jun Liang Yi Zhang Xue‐Qing Liu Wen‐Fei Wang Hai‐Xue Kuang Yong‐Gang Xia Phytotherapy Research A Small Molecular Weight Saccharide Fraction From Panax quinquefolium L. Inhibited Non‐Small Cell Lung Cancer via Endoplasmic Reticulum‐Stress Mediated Apoptosis Jia‐Lu Lü Jun Liang Yi Zhang Xue‐Qing Liu Wen‐Fei Wang Hai‐Xue Kuang Yong‐Gang Xia Phytotherapy Research ABSTRACTNon‐small cell lung cancer remains a significant global health challenge. The limited efficacy, drug resistance, and toxicity of current treatments highlight the need for novel therapeutics. While Panax quinquefolium L. has demonstrated anti‐tumor activity in previous studies, the therapeutic potential of its small molecular weight saccharide fraction (SFPQ) remains unexplored. This study investigates the anti‐tumor efficacy and mechanisms of SFPQ, aiming to establish its potential as a novel anti‐cancer agent. SFPQ was isolated via macroporous resin adsorption and ultrafiltration, then characterized by LC–MS/MS analysis. In vitro cytotoxicity was assessed using CCK‐8 and colony formation assays, and apoptosis was quantified via flow cytometry. Live‐cell fluorescent labeling and confocal microscopy confirmed the specificity of SFPQ for the endoplasmic reticulum. Mechanistic insights into endoplasmic reticulum stress were elucidated via bioinformatics analysis, Western blot, and RT‐qPCR assays. Lentiviral transduction and pharmacological inhibition validated SFPQ‐mediated regulation of IRE1/JNK phosphorylation and c‐Myc expression. In vivo anti‐tumor efficacy and safety were assessed using xenograft models, complemented by morphometric parameters analysis and histopathology. CCK‐8 and colony formation assay demonstrated cytotoxic effects of SFPQ on non‐small cell lung cancer cells. SFPQ significantly promoted endoplasmic reticulum Ca2+ efflux, altered endoplasmic reticulum morphology, and increased the apoptosis rate for A549 cells. Live‐cell imaging confirmed strong endoplasmic reticulum affinity, while mechanistic studies demonstrated that SFPQ triggered endoplasmic reticulum stress‐mediated apoptosis via the IRE1/JNK/c‐Myc axis. In xenograft models, SFPQ significantly reduced tumor volume and weight in a dose‐dependent manner, showing comparable efficacy to cisplatin. Histopathological analysis further confirmed SFPQ's favorable safety profile. This study elucidates the endoplasmic reticulum stress‐mediated anti‐lung cancer mechanism of SFPQ through IRE1/JNK/c‐Myc signaling. SFPQ exhibits potent anti‐lung cancer activity in vitro and in vivo with minimal systemic toxicity, supporting its potential as a novel therapeutic agent. 10.1002/ptr.70036 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | A Small Molecular Weight Saccharide Fraction From Panax quinquefolium L. Inhibited Non‐Small Cell Lung Cancer via Endoplasmic Reticulum‐Stress Mediated Apoptosis |
| topic | Phytotherapy Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/ptr.70036 |