Dioscin induces osteosarcoma cell apoptosis by upregulating ROS‐mediated P38 MAPK signaling

Zheng, Guizhou; Zhang, Qi‐hao; Chang, Bo-Jui; Xie, Peng; Liao, Hang; Du, Shasha; Li, Xue‐Dong

doi:10.1002/ddr.22009

Cited by 9 publications

(9 citation statements)

References 32 publications

(40 reference statements)

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“…Among many signaling pathways, MAPK signaling pathway plays a particularly important role in cell proliferation, differentiation, apoptosis, angiogenesis and tumor metastasis [ 29 ]. There is reported that dioscin induces OS cell apoptosis by upregulating ROS-mediated P38 MAPK signaling [ 30 ], and Fan’s research also showed that siglec-15 promotes tumor progression in OS via DUSP1/MAPK pathway [ 31 ]. Similarly, the role of PI3K/AKT pathway in reversing drug resistance in OS is confirmed by the examination of some reports [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

What role does GPR65 play in the progression of osteosarcoma? Its mechanism and clinical significance

Qi,

Liu,

Zhang

2024

Cancer Cell Int

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Background GPR65 is a pH-sensing G-protein-coupled receptor that acts as a key innate immune checkpoint in the human tumor microenvironment, inhibiting the release of inflammatory factors and inducing significant upregulation of tissue repair genes. However, the expression pattern and function of GPR65 in osteosarcoma (OS) remain unclear. The purpose of this study was to investigate and elucidate the role of GPR65 in the microenvironment, proliferation and migration of OS. Methods Retrospective RNA-seq data analysis was conducted in a cohort of 97 patients with OS data in the TAEGET database. In addition, single-cell sequencing data from six surgical specimens of human OS patients was used to analyze the molecular evolution process during OS genesis. Tissues chips and bioinformatics results were used to verify GPR65 expression level in OS. MTT, colony formation, EdU assay, wound healing, transwell assay and F-actin assay were utilized to analyze cell proliferation and invasion of OS cancer cells. RNA-seq was used to explore the potential mechanism of GPR65’s role in OS. Results GPR65 expression was significantly low in OS, and subgroup analysis found that younger OS patients, OS patients in metastatic status, and overall survival and progression free survival OS patients had lower GPR65 expression. From ScRNA-seq data of GSE162454, we found the expression of GPR65 is significantly positively correlated with CD4 + T cells CD8 + T cells and OS related macrophage infiltration. Verification experiment found that silencing the expression of GPR65 in osteosarcoma cells U2OS and HOS could promote the proliferation and invasion process, RNA-seq results showed that the role of GPR65 in OS cells was related to immune system, metabolism and signal transduction. Conclusion The low expression of GPR65 in OS leads to high metastasis rate and poor prognosis in OS patients. The suppression of immune escape and inhibition of proliferation may be a key pathway for GPR65 to participate in the progression of OS. The current study strengthens the role of GPR65 in OS development and provides a potential biomarker for the prognosis of OS patients.

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Section: Discussionmentioning

confidence: 99%

What role does GPR65 play in the progression of osteosarcoma? Its mechanism and clinical significance

Qi,

Liu,

Zhang

2024

Cancer Cell Int

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“…U2OS, HOS [134] Fistein Wood wax U2OS [135] Ginsenoside Rh2 Panax ginseng C. A. Mey. U2OS [136] MAPK pathway Dioscin Dioscorea polystachya Turczaninow MG-63, U2OS [137] Lycorine Lycoris radiata (L'Her.) Herb.…”

Section: Mg-63mentioning

confidence: 99%

“…Zheng et al [137] found that diosgenin inhibited the proliferation, migration and invasion of OS cell, and induced OS cell apoptosis by up-regulating ROS-mediated P38/MAPK signaling pathway. Similarly, studies by Ning L, Yuan XH et al [97,138] found that lycorine was also able to increase the intracellular ROS content, thereby activating the p38-MAPK signaling pathway and inhibiting the expression level of the downstream member p53 protein, which in turn arrested the growth of mouse OS cells in G1 phase, and promoted apoptosis of mouse OS cells.…”

Section: Targeted Therapy Of Os By Signaling Cascade Associated With ...mentioning

confidence: 99%

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

Liu,

Jiang,

et al. 2024

Medicine

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Osteosarcoma (OS) has a high recurrence rate, disability rate, mortality and metastasis, it brings great economic burden and psychological pressure to patients, and then seriously affects the quality of life of patients. At present, the treatment methods of OS mainly include radiotherapy, chemotherapy, surgical therapy and neoadjuvant chemotherapy combined with limb salvage surgery. These treatment methods can relieve the clinical symptoms of patients to a certain extent, and also effectively reduce the disability rate, mortality and recurrence rate of OS patients. However, because metastasis of tumor cells leads to new complications, and OS cells become resistant with prolonged drug intervention, which reduces the sensitivity of OS cells to drugs, these treatments still have some limitations. More and more studies have shown that traditional Chinese medicine (TCM) has the characteristics of “multiple targets and multiple pathways,” and can play an important role in the development of OS through several key signaling pathways, including PI3K/AKT, Wnt/β-catenin, tyrosine kinase/transcription factor 3 (JAK/STAT3), Notch, transforming growth factor-β (TGF-β)/Smad, nuclear transcription factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nuclear factor E2-related factor 2 (Nrf2), Hippo/YAP, OPG/RANK/RANKL, Hedgehog and so on. In this paper, the signaling pathways of cross-interference between active ingredients of TCM and OS were reviewed, and the development status of novel OS treatment was analyzed. The active ingredients in TCM can provide therapeutic benefits to patients by targeting the activity of signaling pathways. In addition, potential strategies for targeted therapy of OS by using ferroptosis were discussed. We hope to provide a unique insight for the in-depth research and clinical application of TCM in the fields of OS growth, metastasis and chemotherapy resistance by understanding the signaling crosstalk between active ingredients in TCM and OS.

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“…N-acetylcysteine is an inhibitor of ROS that can inhibit the apoptosis of diosgenin-related p38/MAPK signal transduction. This indicates that ROS plays an important role in diosgenin-induced apoptosis ( Zheng et al, 2023 ). In addition, the class I HDAC inhibitor MS-275 enhances the vulnerability of ROS in sarcoma cells.…”

Section: Therapeutic Prospect Of Targeting Hif-1α In the Treatment Of...mentioning

confidence: 99%

Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis

Zhou,

Lan,

Liu

et al. 2024

Front. Pharmacol.

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Osteosarcoma (OS) is a malignant tumor originating from mesenchymal tissue. Pulmonary metastasis is usually present upon initial diagnosis, and metastasis is the primary factor affecting the poor prognosis of patients with OS. Current research shows that the ability to regulate the cellular microenvironment is essential for preventing the distant metastasis of OS, and anoxic microenvironments are important features of solid tumors. During hypoxia, hypoxia-inducible factor-1α (HIF-1α) expression levels and stability increase. Increased HIF-1α promotes tumor vascular remodeling, epithelial-mesenchymal transformation (EMT), and OS cells invasiveness; this leads to distant metastasis of OS cells. HIF-1α plays an essential role in the mechanisms of OS metastasis. In order to develop precise prognostic indicators and potential therapeutic targets for OS treatment, this review examines the molecular mechanisms of HIF-1α in the distant metastasis of OS cells; the signal transduction pathways mediated by HIF-1α are also discussed.

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Dioscin induces osteosarcoma cell apoptosis by upregulating ROS‐mediated P38 MAPK signaling

Cited by 9 publications

References 32 publications

What role does GPR65 play in the progression of osteosarcoma? Its mechanism and clinical significance

What role does GPR65 play in the progression of osteosarcoma? Its mechanism and clinical significance

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis

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