Pedunculoside inhibits epithelial-mesenchymal transition and overcomes Gefitinib-resistant non-small cell lung cancer through regulating MAPK and Nrf2 pathways

Fan, Qiumei; Liang, Xiaowei; Xu, Zhao‐Dong; Liu, Siyuan; Han, Shan; Xiao, Yungao; Xu, Qiong; Yuan, Renyikun; Yang, Shilin; Gao, Hongwei

doi:10.1016/j.phymed.2023.154884

Cited by 12 publications

(3 citation statements)

References 51 publications

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“…It has been determined that the BRAF gene is an oncogene of the RAF/MEK/ERK pathway in non-small cell lung cancer (NSCLC), leading to abnormal activation of the pathway [56,57]. Numerous studies have demonstrated that RAF1, a key component of the MAPK signaling cascade, regulates phosphorylation and dephosphorylation in NSCLC cells in a multidirectional manner, opening up new research directions for the investigation of NSCLC pathogenesis [58,59]. According to earlier research, ZEB1 regulation by USP10 is signi cantly in uenced by the MEK-ERK signaling pathway [60].…”

Section: Discussionmentioning

confidence: 99%

USP32 facilitates non-small cell lung cancer progression via deubiquitinating BAG3 and activating RAF-MEK-ERK signaling pathway

李,

Yang,

Ding

et al. 2024

Preprint

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The regulatory significance of ubiquitin-specific peptidase 32 (USP32) in tumor is significant, nevertheless, the biological roles and regulatory mechanisms of USP32 in non-small cell lung cancer (NSCLC) remain unclear. According to our research, USP32 was strongly expressed in NSCLC cell lines and tissues and was linked to a bad prognosis for NSCLC patients. Interference with USP32 resulted in a significant inhibition of NSCLC cell proliferation, migration potential, and EMT development; on the other hand, USP32 overexpression had the opposite effect. To further elucidate the mechanism of action of USP32 in NSCLC, we screened H1299 cells for interacting proteins and found that USP32 interacts with BAG3 (Bcl2-associated athanogene 3) and deubiquitinates and stabilizes BAG3 in a deubiquitinating activity-dependent manner. Functionally, restoration of BAG3 expression abrogated the antitumor effects of USP32 silencing. Furthermore, USP32 increased the phosphorylation level of the RAF/MEK/ERK signaling pathway in NSCLC cells by stabilizing BAG3. In summary, these findings imply that USP32 is critical to the development of NSCLC and could offer a theoretical framework for the clinical diagnosis and management of NSCLC patients in the future.

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Section: Discussionmentioning

confidence: 99%

USP32 facilitates non-small cell lung cancer progression via deubiquitinating BAG3 and activating RAF-MEK-ERK signaling pathway

李,

Yang,

Ding

et al. 2024

Preprint

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“…Subsequent research indicated that gefitinib suppressed the EGFR-ERK/AKT signaling pathway, which activated FOXO3a and lowered ROS levels, thereby obstructing the caspase-independent cell death prompted by cisplatin [ 55 ]. Pedunculoside, a triterpene saponin extracted from Ilex rotunda Thunb, downregulates epithelial-mesenchymal transition (EMT)-related protein expression through the MAPK and NRF2 pathways, decreases ROS production, and counteracts NSCLC metastasis [ 56 ]. Moreover, ROS have been reported to induce tumor growth by upregulating DNMT1 expression and downregulating miR-199a and miR-125b expression, thereby promoting the expression of ErbB2 and ErbB3 [ 57 ].…”

Section: The Ros-mediated Mechanisms Of Cancer Cell Killing By Differ...mentioning

confidence: 99%

Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer

Lin,

Wang,

Diao

et al. 2024

Cancer Cell Int

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Background In tumor treatment, protein tyrosine kinase inhibitors (TKIs) have been extensively utilized. However, the efficacy of TKI is significantly compromised by drug resistance. Consequently, finding an effective solution to overcome TKI resistance becomes crucial. Reactive oxygen species (ROS) are a group of highly active molecules that play important roles in targeted cancer therapy including TKI targeted therapy. In this review, we concentrate on the ROS-associated mechanisms of TKI lethality in tumors and strategies for regulating ROS to reverse TKI resistance in cancer. Main body Elevated ROS levels often manifest during TKI therapy in cancers, potentially causing organelle damage and cell death, which are critical to the success of TKIs in eradicating cancer cells. However, it is noteworthy that cancer cells might initiate resistance pathways to shield themselves from ROS-induced damage, leading to TKI resistance. Addressing this challenge involves blocking these resistance pathways, for instance, the NRF2-KEAP1 axis and protective autophagy, to promote ROS accumulation in cells, thereby resensitizing drug-resistant cancer cells to TKIs. Additional effective approaches inducing ROS generation within drug-resistant cells and providing exogenous ROS stimulation. Conclusion ROS play pivotal roles in the eradication of tumor cells by TKI. Harnessing the accumulation of ROS to overcome TKI resistance is an effective and widely applicable approach. Graphical Abstract

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“…ROS/RNS are relatively unstable physiological molecules that act as second messengers, or intermediaries, in both apoptotic and survival-related cell signalling pathways. ROS-induced pathways (e.g., mitogen-activated protein kinase (MAPK) and protein tyrosine kinase (PTK) cascades), are also known to influence and enhance the metastatic potential of neoplastic cells [29,30].…”

Section: Introductionmentioning

confidence: 99%

The Therapeutic Potential of Oxyhydrogen Gas in Oncology: A Study on Epstein–Barr Virus-Immortalised B-Lymphoblastoid (TK6) Cells

Russell,

Thomas,

Nenov

et al. 2023

Hydrogen

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Cancer is a leading cause of mortality worldwide. B-cells are a keystone of the adaptive immune response and are essential for the presentation of tumor-associated antigens to various types of T-cells. Approximately 1.5% of global cancer cases, including breast and gastric carcinomas and both Hodgkin’s and non-Hodgkin’s lymphomas, are linked with prior Epstein–Barr Virus (EBV) infection. Such properties make EBV-infected lymphocytes ideal models for understanding the effect of oxyhydrogen gas on dysfunctional cell cycling. The aim of this study is to assess the effects of the direct infusion of oxyhydrogen gas on the replicative capacity of EBV-immortalised B-lymphocytes. Oxyhydrogen gas was directly infused into cell culture media. Cells were incubated in 95% air and 5% CO2 for up to 72 h. Cell enumeration was assessed with and without the addition of mitogenic growth stimuli, and subsequent cell-cycle analysis was performed. Cell enumeration: An initial trend of replicative inhibition of TK6 cells is noted with a single oxyhydrogen treatment at the 24 and 48 h time points. The daily addition of oxyhydrogen-infused media showed statistically relevant data at 24 and 48 h but not at 72 h. In mitogen-stimulated cells, a non-statistical trend of inhibition was observed at 24, 48 and 72 h. Analysis details a significant increase in DNA in the Sub G1 phase, indicating increased apoptosis.

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Pedunculoside inhibits epithelial-mesenchymal transition and overcomes Gefitinib-resistant non-small cell lung cancer through regulating MAPK and Nrf2 pathways

Cited by 12 publications

References 51 publications

USP32 facilitates non-small cell lung cancer progression via deubiquitinating BAG3 and activating RAF-MEK-ERK signaling pathway

USP32 facilitates non-small cell lung cancer progression via deubiquitinating BAG3 and activating RAF-MEK-ERK signaling pathway

Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer

The Therapeutic Potential of Oxyhydrogen Gas in Oncology: A Study on Epstein–Barr Virus-Immortalised B-Lymphoblastoid (TK6) Cells

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