Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis

Li, Hui; Wen, Wen; Luo, Jia

doi:10.3390/biomedicines10010108

Cited by 9 publications

(5 citation statements)

References 290 publications

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“…These results may also provide new value for PFD for the treatment of other alcohol-associate diseases. For example, alcohol is a known etiological factor for pancreatitis and pancreatic cancer ( 43 ). As a result, PFD may be a candidate drug for treating alcoholic pancreatitis and associated pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Pirfenidone ameliorates alcohol-induced promotion of breast cancer in mice

Li,

Xu,

Chen

et al. 2024

Front. Oncol.

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PurposeAlcohol consumption increases the risk of breast cancer and promotes cancer progression. Alcohol exposure could affect both processes of the mammary carcinogenesis, namely, the cell transformation and onset of tumorigenesis as well as cancer aggressiveness including metastasis and drug resistance/recurrence. However, the cellular and molecular mechanisms underlying alcohol tumor promotion remain unclear. There are four members of the mammalian p38 mitogen-activated protein kinase (MAPK) family, namely, p38α, p38β, p38γ and p38δ. We have previously demonstrated alcohol exposure selectively activated p38γ MAPK in breast cancer cells in vitro and in vivo. Pirfenidone (PFD), an antifibrotic compound approved for the treatment of idiopathic pulmonary fibrosis, is also a pharmacological inhibitor of p38γ MAPK. This study aimed to determine whether PFD is useful to inhibit alcohol-induced promotion of breast cancer.MethodsFemale adolescent (5 weeks) MMTV-Wnt1 mice were exposed to alcohol with a liquid diet containing 6.7% ethanol. Some mice received intraperitoneal (IP) injection of PFD (100 mg/kg) every other day. After that, the effects of alcohol and PFD on mammary tumorigenesis and metastasis were examined.ResultsAlcohol promoted the progression of mammary tumors in adolescent MMTV-Wnt1 mice. Treatment of PFD blocked tumor growth and alcohol-promoted metastasis. It also significantly inhibited alcohol-induced tumorsphere formation and cancer stem cell (CSC) population.ConclusionPFD inhibited mammary tumor growth and alcohol-promoted metastasis. Since PFD is an FDA-approved drug, the current findings may be helpful to re-purpose its application in treating aggressive breast cancer and alcohol-promoted mammary tumor progression.

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Section: Discussionmentioning

confidence: 99%

Pirfenidone ameliorates alcohol-induced promotion of breast cancer in mice

Li,

Xu,

Chen

et al. 2024

Front. Oncol.

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“…Therapeutics targeting ER stress represent an emerging approach in the treatment of various diseases, particularly those associated with protein misfolding, inflammation, and cellular stress. Since ER is responsible for protein folding and lipid synthesis [78,79], when it becomes overwhelmed due to factors like an excessive buildup of unfolded or misfolded proteins, it triggers a stress response known as the UPR. Prolonged or severe ER stress can lead to cell dysfunction and cell death, contributing to the pathogenesis of several diseases.…”

Section: Targeting Obesity Induced Er Stress Mediator For Cancer Therapymentioning

confidence: 99%

“…For instance, there have been encouraging outcomes observed in treating the condition using methods like small molecule compounds, FDA-approved substances, and gene therapy, all with the goal of re-establishing ER balance. Furthermore, delving deeper into clinical trials and examining each distinct pathway involved, such as the UPR, ERAD, and autophagy, in the context of maintaining or restoring ER equilibrium, holds the potential to uncover innovative therapeutic approaches and possibly identify biomarkers that could predict clinical outcomes [79].…”

Section: Targeting Obesity Induced Er Stress Mediator For Cancer Therapymentioning

confidence: 99%

Impact of Obesity-Related Endoplasmic Reticulum Stress on Cancer and Associated Molecular Targets

AlBashtawi,

Al-Jaber,

Ahmed

et al. 2024

Biomedicines

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Obesity, characterized by excessive body fat, is closely linked to endoplasmic reticulum (ER) stress, leading to insulin resistance and type 2 diabetes. Inflammatory pathways like c-Jun N-terminal kinase (JNK) worsen insulin resistance, impacting insulin signaling. Moreover, ER stress plays a substantial role in cancer, influencing tumor cell survival and growth by releasing factors like vascular endothelial growth factor (VEGF). The unfolded protein response (UPR) is pivotal in this process, offering both pro-survival and apoptotic pathways. This review offers an extensive exploration of the sophisticated connection between ER stress provoked by obesity and its role in both the onset and advancement of cancer. It delves into the intricate interplay between oncogenic signaling and the pathways associated with ER stress in individuals who are obese. Furthermore, this review sheds light on potential therapeutic strategies aimed at managing ER stress induced by obesity, with a focus on addressing cancer initiation and progression. The potential to alleviate ER stress through therapeutic interventions, which may encompass the use of small molecules, FDA-approved medications, and gene therapy, holds great promise. A more in-depth examination of pathways such as UPR, ER-associated protein degradation (ERAD), autophagy, and epigenetic regulation has the potential to uncover innovative therapeutic approaches and the identification of predictive biomarkers.

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“…PSCs are unique resident cells in the pancreas and play important roles in both the healthy and diseased pancreas. The activation of PSCs is a central link in pancreatic fibrogenesis ( Bynigeri et al, 2017 ; Beyer et al, 2020 ; Li et al, 2022 ). PSCs can be activated by multiple triggers, such as ethanol and its metabolites, hyperglycemia, oxidative stress, cytokines, chemokines and stress, and then secrete excessive ECM, which causes interlobular and intralobular fibrosis.…”

Section: Chronic Pancreatitis—risk Factors and Pathogenesismentioning

confidence: 99%

Vitamin D: A Potential Star for Treating Chronic Pancreatitis

Zheng

Gao

2022

Front. Pharmacol.

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Chronic pancreatitis (CP) is a chronic inflammatory and fibrotic disease of the pancreas. The incidence of CP is increasing worldwide but the effective therapies are lacking. Hence, it is necessary to identify economical and effective agents for the treatment of CP patients. Vitamin D (VD) and its analogues have been confirmed as pleiotropic regulators of cell proliferation, apoptosis, differentiation and autophagy. Clinical studies show that VD deficiency is prevalent in CP patients. However, the correlation between VD level and the risk of CP remains controversial. VD and its analogues have been demonstrated to inhibit pancreatic fibrosis by suppressing the activation of pancreatic stellate cells and the production of extracellular matrix. Limited clinical trials have shown that the supplement of VD can improve VD deficiency in patients with CP, suggesting a potential therapeutic value of VD in CP. However, the mechanisms by which VD and its analogues inhibit pancreatic fibrosis have not been fully elucidated. We are reviewing the current literature concerning the risk factors for developing CP, prevalence of VD deficiency in CP, mechanisms of VD action in PSC-mediated fibrogenesis during the development of CP and potential therapeutic applications of VD and its analogues in the treatment of CP.

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Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis

Cited by 9 publications

References 290 publications

Pirfenidone ameliorates alcohol-induced promotion of breast cancer in mice

Pirfenidone ameliorates alcohol-induced promotion of breast cancer in mice

Impact of Obesity-Related Endoplasmic Reticulum Stress on Cancer and Associated Molecular Targets

Vitamin D: A Potential Star for Treating Chronic Pancreatitis

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