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Chinese Journal of Integrative Medicine Mar 2023Cancers have high morbidity and mortality rates worldwide. Current anticancer therapies have demonstrated specific signaling pathways as a target in the involvement of... (Review)
Review
Cancers have high morbidity and mortality rates worldwide. Current anticancer therapies have demonstrated specific signaling pathways as a target in the involvement of carcinogenesis. Autophagy is a quality control system for proteins and plays a fundamental role in cancer carcinogenesis, exerting an anticarcinogenic role in normal cells and can inhibit the transformation of malignant cells. Therefore, drugs aimed at autophagy can function as antitumor agents. Flavonoids are a class of polyphenolic secondary metabolites commonly found in plants and, consequently, consumed in diets. In this review, the systematic search strategy was used, which included the search for descriptors "flavonoids" AND "mTOR pathway" AND "cancer" AND "autophagy", in the electronic databases of PubMed, Cochrane Library, Web of Science and Scopus, from January 2011 to January 2021. The current literature demonstrates that flavonoids have anticarcinogenic properties, including inhibition of cell proliferation, induction of apoptosis, autophagy, necrosis, cell cycle arrest, senescence, impaired cell migration, invasion, tumor angiogenesis and reduced resistance to multiple drugs in tumor cells. We demonstrate the available evidence on the roles of flavonoids and autophagy in cancer progression and inhibition. (Registration No. CRD42021243071 at PROSPERO).
Topics: Humans; Flavonoids; Neoplasms; Antineoplastic Agents; Signal Transduction; Apoptosis; Cell Proliferation; Carcinogenesis; Cell Line, Tumor
PubMed: 35809179
DOI: 10.1007/s11655-022-3674-9 -
Journal of Cancer Research and Clinical... Jan 2024Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) displays distinct epidemiological, clinical, and molecular characteristics compared to... (Review)
Review
PURPOSE
Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) displays distinct epidemiological, clinical, and molecular characteristics compared to the negative counterpart. Alterations in autophagy play an important role in cancer, and emerging evidence indicates an interplay of autophagy in HNSCC carcinogenesis and tumor promotion. However, the influence of HPV infection on autophagy in HNSCC has received less attention and has not been previously reviewed. Therefore, we here aimed to systematically review the role of autophagy explicitly in HPV HNSCC.
METHODS
Studies accessible in PubMed, Embase, Scopus, and Web of Science investigating HNSCC, highlighting the molecular biological differences between HPV and HPV HNSCC and its influences on autophagy in HNSCC were analyzed according to the PRISMA statement. A total of 10 articles were identified, included, and summarized.
RESULTS
The HPV16 E7 oncoprotein was reported to be involved in the degradation of AMBRA1 and STING, and to enhance chemotherapy-induced cell death via lethal mitophagy in HNSCC cells. Autophagy-associated gene signatures correlated with HPV-subtype and overall survival. Additionally, immunohistochemical (IHC) analyses indicate that high LC3B expression correlates with poor overall survival in oropharyngeal HNSCC patients.
CONCLUSION
HPV may dampen general bulk autophagic flux via degradation of AMBRA1 but may promote selective autophagic degradation of STING and mitochondria. Interpretations of correlations between autophagy-associated gene expressions or IHC analyses of autophagy-related (ATG) proteins in paraffin embedded tissue with clinicopathological features without biological validation need to be taken with caution.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Papillomavirus Infections; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Autophagy; Adaptor Proteins, Signal Transducing
PubMed: 38291202
DOI: 10.1007/s00432-023-05514-3 -
Mathematical Biosciences and... Jul 2019p62/SQSTM1 is the scaffold protein implicated in selective autophagy, which is induced by cellular stress. Research has shown that p62 is highly expressed in cancer.... (Meta-Analysis)
Meta-Analysis
p62/SQSTM1 is the scaffold protein implicated in selective autophagy, which is induced by cellular stress. Research has shown that p62 is highly expressed in cancer. Moreover, p62 can easily promote tumor metastasis. However, studies have not reached a consensus on the relationship of p62 expression with the diagnosis and prognosis of lung cancer. We conducted a systematic review and meta-analysis of studies on p62 expression in the prognosis and clinical-pathological parameters of lung cancer patients. Literature search was performed with PubMed, Web of Science, EMBASE, Cochrane Library, and SpringerLink databases. Fixed-effects and random-effects models were used to study the relationship of p62 expression with patients' overall survival (OS) and clinical-pathological parameters. I2 was used to test for heterogeneity. Egger's test was used to assess publication bias. The meta-analysis collected and considered 13 articles, which included 1393 lung cancer patients. The studies show that the high expression of p62 is associated with poor OS in lung cancer patients. The clinical-pathological parameters of patients show that p62 is more highly expressed in high TNM stage (II + III + IV VS. I), Lymph node metastasis (N1 VS. N0), and distant metastases (D1 VS. D0). However, there is no correlation between the p62 expression and the Beclin 1 and LC3B in lung cancer patients. In conclusion, the over-expression of p62 is associated with poor OS in lung cancer patients and can be used as a biomarker for lung cancer diagnosis and prognosis.
Topics: Autophagy; Beclin-1; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Microtubule-Associated Proteins; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Sequestosome-1 Protein; Treatment Outcome
PubMed: 31698589
DOI: 10.3934/mbe.2019340 -
Biomolecules Sep 2022Prostate cancer is one of the leading causes of death for men worldwide. The development of resistance, toxicity, and side effects of conventional therapies have made... (Review)
Review
Prostate cancer is one of the leading causes of death for men worldwide. The development of resistance, toxicity, and side effects of conventional therapies have made prostate cancer treatment become more intensive and aggressive. Many phytochemicals isolated from plants have shown to be tumor cytotoxic. In vitro laboratory studies have revealed that natural compounds can affect cancer cell proliferation by modulating many crucial cellular signaling pathways frequently dysregulated in prostate cancer. A multitude of natural compounds have been found to induce cell cycle arrest, promote apoptosis, inhibit cancer cell growth, and suppress angiogenesis. In addition, combinatorial use of natural compounds with hormone and/or chemotherapeutic drugs seems to be a promising strategy to enhance the therapeutic effect in a less toxic manner, as suggested by pre-clinical studies. In this context, we systematically reviewed the currently available literature of naturally occurring compounds isolated from vegetables, fruits, teas, and herbs, with their relevant mechanisms of action in prostate cancer. As there is increasing data on how phytochemicals interfere with diverse molecular pathways in prostate cancer, this review discusses and emphasizes the implicated molecular pathways of cell proliferation, cell cycle control, apoptosis, and autophagy as important processes that control tumor angiogenesis, invasion, and metastasis. In conclusion, the elucidation of the natural compounds' chemical structure-based anti-cancer mechanisms will facilitate drug development and the optimization of drug combinations. Phytochemicals, as anti-cancer agents in the treatment of prostate cancer, can have significant health benefits for humans.
Topics: Antineoplastic Agents; Apoptosis; Hormones; Humans; Male; Neovascularization, Pathologic; Phytochemicals; Prostatic Neoplasms
PubMed: 36139145
DOI: 10.3390/biom12091306 -
Frontiers in Pharmacology 2023Cancer is a disease with a high fatality rate representing a serious threat to human health. Researchers have tried to identify effective anticancer drugs. Licorice is a...
Cancer is a disease with a high fatality rate representing a serious threat to human health. Researchers have tried to identify effective anticancer drugs. Licorice is a widely used traditional Chinese medicine with various pharmacological properties, and licorice-derived flavonoids include licochalcones like licochalcone A, licochalcone B, licochalcone C, licochalcone D, licochalcone E, and licochalcone H. By regulating the expression in multiple signaling pathways such as the EGFR/ERK, PI3K/Akt/mTOR, p38/JNK, JAK2/STAT3, MEK/ERK, Wnt/β-catenin, and MKK4/JNK pathways, and their downstream proteins, licochalcones can activate the mitochondrial apoptosis pathway and death receptor pathway, promote autophagy-related protein expression, inhibit the expression of cell cycle proteins and angiogenesis factors, regulate autophagy and apoptosis, and inhibit the proliferation, migration, and invasion of cancer cells. Among the licochalcones, the largest number of studies examined licochalcone A, far more than other licochalcones. Licochalcone A not only has prominent anticancer effects but also can be used to inhibit the efflux of antineoplastic drugs from cancer cells. Moreover, derivatives of licochalcone A exhibit strong antitumor effects. Currently, most results of the anticancer effects of licochalcones are derived from cell experiments. Thus, more clinical studies are needed to confirm the antineoplastic effects of licochalcones.
PubMed: 36755942
DOI: 10.3389/fphar.2023.1074506 -
Phytomedicine : International Journal... Jul 2024Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis is a novel type of... (Review)
Review
BACKGROUND
Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis is a novel type of iron-dependent programmed cell death, distinct from apoptosis, necroptosis, and autophagy, characterised by iron, reactive oxygen species, and lipid peroxide accumulation, as well as glutathione (GSH) depletion and GSH peroxidase 4 (GPX4) inactivation. A close association between ferroptosis and the onset and progression of respiratory diseases, including chronic obstructive pulmonary disease, acute lung injury, bronchial asthma, pulmonary fibrosis, and lung cancer, has been reported. Recent studies have shown that traditional Chinese medicine (TCM) compounds exhibit unique advantages in the treatment of respiratory diseases owing to their natural properties and potential efficacy. These compounds can effectively regulate ferroptosis by modulating several key signalling pathways such as system Xc -GSH-GPX4, NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1, thus playing a positive role in improving respiratory diseases.
PURPOSE
This comprehensive review systematically outlines the regulatory role of ferroptosis in the onset and progression of respiratory diseases and provides evidence for treating respiratory diseases by targeting ferroptosis with TCM compounds. These insights aim to offer potential remedies for the clinical prevention and treatment of respiratory diseases.
STUDY DESIGN AND METHODS
We searched scientific databases PubMed, Web of Science, Scopus, and CNKI using keywords such as "ferroptosis","respiratory diseases","chronic obstructive pulmonary disease","bronchial asthma","acute lung injury","pulmonary fibrosis","lung cancer","traditional Chinese medicine","traditional Chinese medicine compound","monomer", and "natural product" to retrieve studies on the therapeutic potential of TCM compounds in ameliorating respiratory diseases by targeting ferroptosis. The retrieved data followed PRISMA criteria (preferred reporting items for systematic review).
RESULTS
TCM compounds possess unique advantages in treating respiratory diseases, stemming from their natural origins and proven clinical effectiveness. TCM compounds can exert therapeutic effects on respiratory diseases by regulating ferroptosis, which mainly involves modulation of pathways such as system Xc -GSH-GPX4,NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1.
CONCLUSION
TCM compounds have demonstrated promising potential in improving respiratory diseases through the regulation of ferroptosis. The identification of specific TCM-related inducers and inhibitors of ferroptosis holds great significance in developing more effective strategies. However, current research remains confined to animal and cellular studies, emphasizing the imperative for further verifications through high-quality clinical data.
Topics: Ferroptosis; Humans; Drugs, Chinese Herbal; Animals; Signal Transduction; Acute Lung Injury; Medicine, Chinese Traditional; Respiratory Tract Diseases; Reactive Oxygen Species; Pulmonary Fibrosis
PubMed: 38824825
DOI: 10.1016/j.phymed.2024.155738 -
Frontiers in Neuroscience 2023Spinal cord injury (SCI) is a catastrophic condition with few therapeutic options. Astaxanthin (AST), a natural nutritional supplement with powerful antioxidant...
Spinal cord injury (SCI) is a catastrophic condition with few therapeutic options. Astaxanthin (AST), a natural nutritional supplement with powerful antioxidant activities, is finding its new application in the field of SCI. Here, we performed a systematic review to assess the neurological roles of AST in rats following SCI, and assessed the potential for clinical translation. Searches were conducted on PubMed, Embase, Cochrane Library, the Web of Science, China National Knowledge Infrastructure, WanFang data, Vip Journal Integration Platform, and SinoMed databases. Animal studies that evaluated the neurobiological roles of AST in a rat model of SCI were included. A total of 10 articles were included; most of them had moderate-to-high methodological quality, while the overall quality of evidence was not high. Generally, the meta-analyses revealed that rats treated with AST exhibited an increased Basso, Beattie, and Bresnahan (BBB) score compared with the controls, and the weighted mean differences (WMDs) between those two groups showed a gradual upward trend from days 7 (six studies, n = 88, WMD = 2.85, 95% CI = 1.83 to 3.87, < 0.00001) to days 28 (five studies, n = 76, WMD = 6.42, 95% CI = 4.29 to 8.55, < 0.00001) after treatment. AST treatment was associated with improved outcomes in spared white matter area, motor neuron survival, and SOD and MDA levels. Subgroup analyses indicated there were differences in the improvement of BBB scores between distinct injury types. The trial sequential analysis then firmly proved that AST could facilitate the locomotor recovery of rats following SCI. In addition, this review suggested that AST could modulate oxidative stress, neuroinflammation, neuron loss, and autophagy multiple signaling pathways for treating SCI. Collectively, with a protective effect, good safety, and a systematic action mechanism, AST is a promising candidate for future clinical trials of SCI. Nonetheless, in light of the limitations of the included studies, larger and high-quality studies are needed for verification.
PubMed: 37881327
DOI: 10.3389/fnins.2023.1255755 -
Nutrients Jul 2020Choline is an essential micronutrient with a pivotal role in several metabolic pathways contributing to liver, neurological, and hematological homeostasis. Although... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Choline is an essential micronutrient with a pivotal role in several metabolic pathways contributing to liver, neurological, and hematological homeostasis. Although choline is commonly administered to improve physical performance, its effects on muscle are still unclear. The aim of this scoping review is to analyze the role of choline on skeletal muscle in terms of biological effects and clinical implications.
METHODS
A technical expert panel (TEP) of 6 medical specialists with expertise in muscle physiology and skeletal muscle disorders performed the review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model. The TEP planned a research on PubMed selecting "choline" as MeSH (Medical Subject Headings) term adding to PubMed Search Builder the terms "skeletal muscle" and "muscle striated". TEP considered for eligibility articles published in the last 30 years, including original researches, particularly in vitro studies, and animal and clinical studies in the English language.
RESULTS
From the 1239 studies identified, TEP included 14 studies, 3 in vitro, 9 animal, and 2 clinical studies.
CONCLUSIONS
Our scoping review elucidates and summarizes the crucial role of choline in modulating muscle fat metabolism, muscle proteins homeostasis, and the modulation of inflammation and autophagy.
Topics: Adipose Tissue; Animals; Autophagy; Calcium; Choline; Eating; Humans; Inflammation; Muscle Proteins; Muscle, Skeletal; Nutritional Physiological Phenomena; Physical Functional Performance; Vitamin B Complex
PubMed: 32708497
DOI: 10.3390/nu12072144 -
Plants (Basel, Switzerland) Dec 2021The objective of this study was to carry out a systematic review of the substances isolated from the African medicinal plant focusing on compounds harboring activities... (Review)
Review
The objective of this study was to carry out a systematic review of the substances isolated from the African medicinal plant focusing on compounds harboring activities against cancer models detailed in depth herein at both in vitro and in vivo preclinical levels. The review was conducted through Pubmed and Google Scholar. Nineteen out of the forty-two secondary metabolites isolated to date from displayed interesting in vitro and/or in vivo antitumor activities. They belonged to alkaloid (Erysodine), triterpenes (Erythrodiol, maniladiol, oleanolic acid), prenylated isoflavonoids (senegalensin, erysenegalensein E, erysenegalensein M, alpinumisoflavone, derrone, warangalone), flavonoids (erythrisenegalone, senegalensein, lupinifolin, carpachromene) and pterocarpans (erybraedine A, erybraedine C, phaseollin). Among the isoflavonoids called "erysenegalensein", only erysenealenseins E and M have been tested for their anticancerous properties and turned out to be cytotoxic. Although the stem bark is the most frequently used part of the plant, all pterocarpans were isolated from roots and all alkaloids from seeds. The mechanisms of action of its metabolites include apoptosis, pyroptosis, autophagy and mitophagy via the modulation of cytoplasmic proteins, miRNA and enzymes involved in critical pathways deregulated in cancer. Alpinumisoflavone and oleanolic acid were studied in a broad spectrum of cancer models both in vitro and in preclinical models in vivo with promising results. Other metabolites, including carpachromen, phaseollin, erybraedin A, erysenegalensein M and maniladiol need to be further investigated, as they display potent in vitro effects.
PubMed: 35009024
DOI: 10.3390/plants11010019 -
Biomedicine & Pharmacotherapy =... Jun 2022Ovarian cancer is mostly diagnosed at an advanced stage due to the absence of effective screening methods and specific symptoms. Repeated chemotherapy resistance and... (Review)
Review
Ovarian cancer is mostly diagnosed at an advanced stage due to the absence of effective screening methods and specific symptoms. Repeated chemotherapy resistance and recurrence before PARPi are used as maintenance therapies, lead to low survival rates and poor prognosis. Apoptotic cell death plays a crucial role in ovarian cancer, which is proved by current researches. With the ongoing development of targeted therapy, non-apoptotic cell death has shown substantial potential in tumor prevention and treatment, including autophagy, ferroptosis, necroptosis, immunogenic cell death, pyroptosis, alkaliptosis, and other modes of cell death. We systematically reviewed the research progress on the role of non-apoptotic cell death in the onset, development, and outcome of ovarian cancer. This review provides a more theoretical basis for exploring therapeutic targets, reversing drug resistance in refractory ovarian cancer, and establishing risk prediction models that help realize the clinical transformation of vital drugs.
Topics: Apoptosis; Carcinoma, Ovarian Epithelial; Female; Ferroptosis; Humans; Necroptosis; Ovarian Neoplasms; Pyroptosis
PubMed: 35429741
DOI: 10.1016/j.biopha.2022.112929