A polysaccharide from Hedyotis diffusa interrupts metastatic potential of lung adenocarcinoma A549 cells by inhibiting EMT via EGFR/Akt/ERK signaling pathways

Lin, Liyao; Cheng, Kun; He, Zhan; Lin, Qian; Huang, Yongye; Chen, Chun-Yuan; Xie, Zhanqiang; Chen, Lin; Zhu, Liang

doi:10.1016/j.ijbiomac.2019.02.040

Cited by 20 publications

(9 citation statements)

References 38 publications

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“…All cells were cultured as monolayers and maintained in a cell culture incubator at 37°C and 5% CO 2 . Previous literature research revealed that the main active components of ginseng in the treatment of lung adenocarcinoma were ginsenosides (such as ginsenoside Rh2/Rh3) and polysaccharides [ 19 – 21 ], with ginsenoside and polysaccharide used as the medicated group and cyclophosphamide used as the positive control group in the cell experiments.…”

Section: Methodsmentioning

confidence: 99%

Study on the Mechanism of Ginseng in the Treatment of Lung Adenocarcinoma Based on Network Pharmacology

Hou

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Background. Ginseng, a traditional Chinese medicine, was used to prevent and treat many diseases such as diabetes, inflammation, and cancer. In recent years, there are some reports about the treatment of lung adenocarcinoma with ginseng monomer compounds, but there is no systematic study on the related core targets and mechanism of ginseng in the treatment of lung adenocarcinoma up to now. Therefore, this study systematically and comprehensively studied the molecular mechanism of ginseng in the treatment of lung adenocarcinoma based on network pharmacology and further proved the potential targets by A549 cell experiments for the first time. Methods. The targets of disease and drug were obtained from Gene database. Subsequently, the compound-target network was constructed, and the core potential targets were screened out by plug-in into Cytoscape. Furthermore, the core targets and mechanism of ginseng in the treatment of lung adenocarcinoma were verified by MTT test, cell scratch test, immunohistochemistry, and qRT-PCR. Results. 1791 disease targets and 144 drug targets were obtained by searching the Gene database. Meanwhile, 15 core targets were screened out: JUN, MAPK8, PTGS2, CASP3, VEGFA, MMP9, AKT1, TNF, FN1, FOS, MMP782, IL-1β, IL-2, ICAM1, and HMOX1. The results of cell experiments indicate that ginseng could treat lung adenocarcinoma by cell proliferation, migration, and apoptosis. In addition, according to the results of the 15 core targets by qRT-PCR, JUN, IL-1β, IL-2, ICAM1, HMOX1, MMP9, and MMP2 are upregulated core targets, while PTGS2 and TNF are downregulated core targets. Conclusion. This study systematically and comprehensively studied 15 core targets by network pharmacology for the first time. Subsequently, it is verified that 9 core targets for ginseng treatment of lung adenocarcinoma, namely, JUN, IL-1β, IL-2, ICAM1, HMOX1, MMP9, MMP2, PTGS2, and TNF, are closely related to the proliferation, migration, and apoptosis of lung adenocarcinoma cells. This study has reference value for the clinical application of ginseng in the treatment of lung adenocarcinoma.

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Section: Methodsmentioning

confidence: 99%

Study on the Mechanism of Ginseng in the Treatment of Lung Adenocarcinoma Based on Network Pharmacology

Hou

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…The ethanol extract of Hedyotis diffusa could significantly limit the proliferation and induce apoptosis of highly metastatic breast cancer cells MDA-MB-231 and MDA-MB-453, but had no obvious cytotoxic effect on a variety of non-malignant cells ( Yang et al, 2019 ). Hedyotis diffusa polysaccharide inhibited cell adhesion, invasion and migration of human lung adenocarcinoma A549 cells by downregulating matrix metalloproteinase ( Lin et al, 2019 ). Tulip improves the sensitivity of tumor-resistant cells to doxorubicin and docetaxel by downregulating the expression of P-gp and inducing S-phase arrest ( Yang et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Autophagy Blockade by Ai Du Qing Formula Promotes Chemosensitivity of Breast Cancer Stem Cells Via GRP78/β-Catenin/ABCG2 Axis

et al. 2021

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Accumulating evidence suggests that the root of drug chemoresistance in breast cancer is tightly associated with subpopulations of cancer stem cells (CSCs), whose activation is largely dependent on taxol-promoting autophagy. Our pilot study identified GRP78 as a specific marker for chemoresistance potential of breast CSCs by regulating Wnt/β-catenin signaling. Ai Du Qing (ADQ) is a traditional Chinese medicine formula that has been utilized in the treatment cancer, particularly during the consolidation phase. In the present study, we investigated the regulatory effects and molecular mechanisms of ADQ in promoting autophagy-related breast cancer chemosensitivity. ADQ with taxol decreasing the cell proliferation and colony formation of breast cancer cells, which was accompanied by suppressed breast CSC ratio, limited self-renewal capability, as well as attenuated multi-differentiation. Furthermore, autophagy in ADQ-treated breast CSCs was blocked by taxol via regulation of β-catenin/ABCG2 signaling. We also validated that autophagy suppression and chemosensitizing activity of this formula was GRP78-dependent. In addition, GRP78 overexpression promoted autophagy-inducing chemoresistance in breast cancer cells by stabilizing β-catenin, while ADQ treatment downregulated GRP78, activated the Akt/GSK3β-mediated proteasome degradation of β-catenin via ubiquitination activation, and consequently attenuated the chemoresistance-promoted effect of GRP78. In addition, both mouse breast cancer xenograft and zebrafish xenotransplantation models demonstrated that ADQ inhibited mammary tumor growth, and the breast CSC subpopulation showed obscure adverse effects. Collectively, this study not only reveals the chemosensitizating mechanism of ADQ in breast CSCs, but also highlights the importance of GRP78 in mediating autophagy-promoting drug resistance via β-catenin/ABCG2 signaling.

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“…SRC activation is associated with chemotherapy and EGFR antibody resistance, which has led to the strategy of developing SRC family-specific inhibitors to prevent immune inhibition (46). Research on NPCs targeting EGFR has remained important (48). The ligands of EGFR (EGF and TGF-α) bind to its extracellular domain and induce phosphorylation of its intracellular domain, in turn activating an intricate downstream signalling pathway (49,50) Curcumin treatment has been found to significantly reduce the proliferation and migration of NSCLC cells, possibly through toll-like receptor 4/myeloid differentiation primary response protein MyD88-EGFR-mediated inhibition of AP-1 protein and suppression of the EMT process (51).…”

Section: Discussionmentioning

confidence: 99%

Fangchinoline exerts antitumour activity by suppressing the EGFR‑PI3K/AKT signalling pathway in colon adenocarcinoma

et al. 2020

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Fangchinoline (FAN), an alkaloid extracted from Stephania tetrandra , has a variety of biological and pharmacological activities, but evidence of its effects on colon adenocarcinoma (COAD) is limited. Therefore, the present study aimed to elucidate the molecular mechanisms by which FAN affects COAD. The cytotoxicity, viability and proliferation of DLD-1 and LoVo cells were assessed in the presence of FAN using MTT and colony formation assays. The effects of FAN on apoptosis and the cell cycle in COAD cells were analysed by flow cytometry, and the migration and invasion of these cells were assessed by wound healing and Transwell experiments. Furthermore, a network pharmacological analysis was conducted to investigate the target of FAN and the results were confirmed by western blotting. In addition, a xenograft model was established in nude mice, and ultrasound imaging was used to assess the preclinical therapeutic effects of FAN in vivo . To the best of our knowledge, the results of this study provided the first evidence that FAN inhibited cellular proliferation, stemness, migration, invasion, angiogenesis and epithelial-mesenchymal transition (EMT), and induced apoptosis and G1-phase cell cycle arrest. Network pharmacological analysis further confirmed that FAN prevented EMT through the epidermal growth factor receptor (EGFR)-phosphoinositide 3-kinase (PI3K)/AKT signalling pathway. Finally, FAN significantly repressed tumour growth and promoted apoptosis in xenografts. Thus, targeting EGFR with FAN may offer a novel therapeutic approach for COAD.

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A polysaccharide from Hedyotis diffusa interrupts metastatic potential of lung adenocarcinoma A549 cells by inhibiting EMT via EGFR/Akt/ERK signaling pathways

Cited by 20 publications

References 38 publications

Study on the Mechanism of Ginseng in the Treatment of Lung Adenocarcinoma Based on Network Pharmacology

Study on the Mechanism of Ginseng in the Treatment of Lung Adenocarcinoma Based on Network Pharmacology

Autophagy Blockade by Ai Du Qing Formula Promotes Chemosensitivity of Breast Cancer Stem Cells Via GRP78/β-Catenin/ABCG2 Axis

Fangchinoline exerts antitumour activity by suppressing the EGFR‑PI3K/AKT signalling pathway in colon adenocarcinoma

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