Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer DOI Creative Commons

Xuening Pang,

Xiaoyi Zhang, Yuhuan Jiang

et al.

Biomolecules, Journal Year: 2021, Volume and Issue: 11(2), P. 135 - 135

Published: Jan. 21, 2021

Autophagy, which is a conserved biological process and essential mechanism in maintaining homeostasis metabolic balance, enables cells to degrade cytoplasmic constituents through lysosomes, recycle nutrients, survive during starvation. Autophagy exerts an anticarcinogenic role normal inhibits the malignant transformation of cells. On other hand, aberrations autophagy are involved gene derangements, cell metabolism, tumor immune surveillance, invasion metastasis, drug-resistance. Therefore, autophagy-targeted drugs may function as anti-tumor agents. Accumulating evidence suggests that flavonoids have properties, including those relating cellular proliferation inhibition, induction apoptosis, autophagy, necrosis, cycle arrest, senescence, impairment migration, invasion, angiogenesis, reduction multidrug resistance Flavonoids, group natural polyphenolic compounds characterized by multiple targets participate pathways, been widely studied different models for modulation. However, flavonoid-induced commonly interacts with mechanisms, comprehensively influencing anticancer effect. Accordingly, targeted become core treatment tumors. This paper reviews their interaction so provide comprehensive in-depth account on how exert tumor-suppressive effects autophagy.

Language: Английский

Regulated cell death (RCD) in cancer: key pathways and targeted therapies DOI Creative Commons
Peng Fu,

Minru Liao,

Rui Qin

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Aug. 13, 2022

Regulated cell death (RCD), also well-known as programmed (PCD), refers to the form of that can be regulated by a variety biomacromolecules, which is distinctive from accidental (ACD). Accumulating evidence has revealed RCD subroutines are key features tumorigenesis, may ultimately lead establishment different potential therapeutic strategies. Hitherto, targeting with pharmacological small-molecule compounds been emerging promising avenue, rapidly progressed in many types human cancers. Thus, this review, we focus on summarizing not only apoptotic and autophagy-dependent signaling pathways, but crucial pathways other subroutines, including necroptosis, pyroptosis, ferroptosis, parthanatos, entosis, NETosis lysosome-dependent (LCD) cancer. Moreover, further discuss current situation several improve cancer treatment, such single-target, dual or multiple-target compounds, drug combinations, some new strategies would together shed light future directions attack vulnerabilities drugs for purposes.

Language: Английский

Citations

518
Ferritinophagy-mediated ferroptosis is involved in sepsis-induced cardiac injury DOI Creative Commons
Ning Li, Wei Wang, Heng Zhou

et al.

Free Radical Biology and Medicine, Journal Year: 2020, Volume and Issue: 160, P. 303 - 318

Published: Aug. 23, 2020

Ferroptosis is a reactive oxygen species (ROS)- and iron-dependent form of regulated cell death (RCD), playing critical roles in organ injury targeting therapy cancers. Previous studies have demonstrated that ferroptosis participates the development cardiomyopathy including cardiac hypertrophy, diabetic doxorubicin-induced cardiotoxicity. However, role sepsis-induced remains unclear. This study aimed to explore underlying mechanism on lipopolysaccharide (LPS)-induced injury. Mice were injected with LPS (10 mg/kg) for 12 h generate experimental sepsis. Ferrostatin-1 (Fer-1) Dexrazoxane (DXZ) used suppress mice increased levels ferroptotic markers involving prostaglandin endoperoxide synthase 2 (PTGS2), malonaldehyde (MDA) lipid ROS, apart from resulting obvious mitochondria damage, which alleviated by Fer-1 DXZ. In vitro experiments showed inhibited LPS-induced peroxidation H9c2 myofibroblasts while erastin sorafenib aggravated ferroptosis. Additionally, DXZ improved survival rate function Mechanistically, expression nuclear receptor coactivator 4 (NCOA4) level intracellular Fe2+ but decreased ferritin. NCOA4 could directly interact ferritin degrade it ferritinophagy-dependent manner, subsequently released great amount iron. Cytoplasmic further activated siderofexin (SFXN1) mitochondrial membrane, turn transported cytoplasmic into mitochondria, giving rise production ROS Based these findings, we concluded ferritinophagy-mediated one mechanisms contributing Targeting cardiomyocytes may be therapeutic strategy preventing sepsis future.

Language: Английский

Citations

504
Leveraging diverse cell-death patterns to predict the prognosis and drug sensitivity of triple-negative breast cancer patients after surgery DOI Creative Commons
Yutian Zou, Jindong Xie, Shaoquan Zheng

et al.

International Journal of Surgery, Journal Year: 2022, Volume and Issue: 107, P. 106936 - 106936

Published: Sept. 20, 2022

Postoperative progression and chemotherapy resistance is the major cause of treatment failure in patients with triple-negative breast cancer (TNBC). Currently, there a lack an ideal predictive model for drug sensitivity postoperative TNBC patients. Diverse programmed cell death (PCD) patterns play important role tumor progression, which has potential to be prognostic indicator after surgery.Twelve PCD (apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic death, netotic parthanatos, lysosome-dependent autophagy-dependent alkaliptosis, oxeiptosis) were analyzed construction. Bulk transcriptome, single-cell genomics, clinical information collected from TCGA-BRCA, METABRIC, GSE58812, GSE21653, GSE176078, GSE75688, KM-plotter cohorts validate model.The machine learning algorithm established index (CDI) 12-gene signature. Validated five independent datasets, high CDI had worse prognosis surgery. Two molecular subtypes distinct vital biological processes identified by unsupervised clustering model. A nomogram performance was constructed incorporating features. Furthermore, associated immune checkpoint genes key microenvironment components integrated analysis bulk transcriptome. are resistant standard adjuvant regimens (docetaxel, oxaliplatin, etc.); however, they might sensitive palbociclib (an FDA-approved luminal cancer).Generally, we novel comprehensively analyzing diverse patterns, can accurately predict user-friendly website created facilitate application this prediction (https://tnbc.shinyapps.io/CDI_Model/).

Language: Английский

Citations

279
Elucidating the mechanisms of Temozolomide resistance in gliomas and the strategies to overcome the resistance. DOI
Manendra Singh Tomar, Ashok Kumar, Chhitij Srivastava

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2021, Volume and Issue: 1876(2), P. 188616 - 188616

Published: Aug. 20, 2021

Language: Английский

Citations

216
Tumor biomarkers for diagnosis, prognosis and targeted therapy DOI Creative Commons
Yue Zhou, Lei Tao, Jiahao Qiu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 20, 2024

Abstract Tumor biomarkers, the substances which are produced by tumors or body’s responses to during tumorigenesis and progression, have been demonstrated possess critical encouraging value in screening early diagnosis, prognosis prediction, recurrence detection, therapeutic efficacy monitoring of cancers. Over past decades, continuous progress has made exploring discovering novel, sensitive, specific, accurate tumor significantly promoted personalized medicine improved outcomes cancer patients, especially advances molecular biology technologies developed for detection biomarkers. Herein, we summarize discovery development including history conventional innovative used biomarker classification biomarkers based on tissue origins, application clinical management. In particular, highlight recent advancements biomarker-based anticancer-targeted therapies emerging as breakthroughs promising strategies. We also discuss limitations challenges that need be addressed provide insights perspectives turn into opportunities this field. Collectively, multiple emphasized review may guidance precision medicine, broaden horizons future research directions, expedite patients according their rather than organs origin.

Language: Английский

Citations

185
Mechanism of interaction between autophagy and apoptosis in cancer DOI
Shreya Das, Nidhi Shukla, Shashi Shekhar Singh

et al.

APOPTOSIS, Journal Year: 2021, Volume and Issue: 26(9-10), P. 512 - 533

Published: Sept. 12, 2021

Language: Английский

Citations

181
ThePI3K/AKTsignalling pathway in inflammation, cell death and glial scar formation after traumatic spinal cord injury: Mechanisms and therapeutic opportunities DOI Creative Commons
Xuegang He, Ying Li, Bo Deng

et al.

Cell Proliferation, Journal Year: 2022, Volume and Issue: 55(9)

Published: June 26, 2022

Abstract Objects Traumatic spinal cord injury (TSCI) causes neurological dysfunction below the injured segment of cord, which significantly impacts quality life in affected patients. The phosphoinositide 3kinase/serine‐threonine kinase (PI3K/AKT) signaling pathway offers a potential therapeutic target for inhibition secondary TSCI. This review summarizes updates concerning role PI3K/AKT Materials and Methods By searching articles related to TSCI field pathway, we summarized mechanisms pathway; also discuss current future treatment methods based on pathway. Results Early apoptosis autophagy after protect body against injury; prolonged inflammatory response leads accumulation pro‐inflammatory factors excessive apoptosis, as well surrounding normal nerve cells, thus aggravating subacute stage injury. Initial glial scar formation phase is protective mechanism TSCI, limits spread damage inflammation. However, mature tissue chronic hinders axon regeneration prevents recovery function. Activation can inhibit TSCI; inhibiting this reduce scar. Conclusion has an important function Inducing activation may be one strategies

Language: Английский

Citations

170
Gene therapy for neurodegenerative disorders: advances, insights and prospects DOI Creative Commons
Wei Chen, Yang Hu, Dianwen Ju

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2020, Volume and Issue: 10(8), P. 1347 - 1359

Published: Jan. 31, 2020

Gene therapy is rapidly emerging as a powerful therapeutic strategy for wide range of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's (PD) and Huntington's (HD). Some early clinical trials have failed to achieve satisfactory effects. Efforts enhance effectiveness are now concentrating on three major fields: identification new vectors, novel targets, reliable delivery routes transgenes. These approaches being assessed closely in preclinical trials, which may ultimately provide treatments patients. Here, we discuss advances challenges gene highlighting promising technologies, future prospects.

Language: Английский

Citations

162
Potential implications of polyphenols on aging considering oxidative stress, inflammation, autophagy, and gut microbiota DOI
Min Wu, Qingying Luo,

Rongxuan Nie

et al.

Critical Reviews in Food Science and Nutrition, Journal Year: 2020, Volume and Issue: 61(13), P. 2175 - 2193

Published: June 4, 2020

Naturally occurring compounds polyphenols are secondary metabolites of plants, comprised several categories, namely, flavonoids, phenolic acids, lignans and stilbenes. The biological aging process is driven by a series interrelated mechanisms, including oxidative stress, inflammation status, autophagy function, through diverse signaling pathways. Moreover, the crucial role gut microbiota in regulating health status was widely demonstrated. In recent years, potential anti-aging benefits have been gaining increasing scientific interest due to their capability modulate damage, inflammation, autophagy, microbiota. This review highlights influence preventing disorders augmenting lifespan based on microbiota, encourages research novel polyphenol-based strategies clinical trials develop nutrition-oriented holistic therapy.

Language: Английский

Citations

147
Targeting Drug Chemo-Resistance in Cancer Using Natural Products DOI Creative Commons
Wamidh H. Talib, Ahmad R. Alsayed, Muna Barakat

et al.

Biomedicines, Journal Year: 2021, Volume and Issue: 9(10), P. 1353 - 1353

Published: Sept. 29, 2021

Cancer is one of the leading causes death globally. The development drug resistance main contributor to cancer-related mortality. cells exploit multiple mechanisms reduce therapeutic effects anticancer drugs, thereby causing chemotherapy failure. Natural products are accessible, inexpensive, and less toxic sources chemotherapeutic agents. Additionally, they have action inhibit various targets involved in resistance. In this review, we summarized basic research clinical applications natural as possible inhibitors for cancer. molecular each product also explained. Diverse biomarkers were sensitive products. P-glycoprotein breast cancer protein can be targeted by a large number On other hand, kinase C topoisomerases most studied studies discussed review will provide solid ground scientists explore use combination therapies overcome targeting mechanisms.

Language: Английский

Citations

142