Cell Survival and Cell Death at the Intersection of Autophagy and Apoptosis: Implications for Current and Future Cancer Therapeutics

ACS Pharmacology & Translational Science, Journal Year: 2021, Volume and Issue: 4(6), P. 1728 - 1746

Published: Nov. 3, 2021

Autophagy and apoptosis are functionally distinct mechanisms for cytoplasmic cellular turnover. While these two pathways distinct, they can also regulate each other, central components of the or autophagy pathway both processes directly. Furthermore, several upstream stress-inducing signaling influence apoptosis. The crosstalk between has an integral role in pathological processes, including those related to cancer, homeostasis, aging. Apoptosis is a form programmed cell death, tightly regulated by various biochemical mechanisms, some which have been focus drug discovery efforts targeting cancer therapeutics. degradation whereby cells recycle macromolecules organelles generate energy when subjected stress. act as either prodeath prosurvival process tissue microenvironment specific. In this review we describe five groups proteins that discuss their regulating autophagy. We highlight apoptosis-inducing small molecules biologics developed advanced into clinic effects on For most part, compounds appear elevate activity. Under certain circumstances demonstrates cytoprotective functions overactivated response chemo- radiotherapy lead resistance, representing clinical obstacle successful treatment. Thus, combination with may be promising strategy therapy.

Language: Английский

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Hepatocyte programmed cell death: the trigger for inflammation and fibrosis in metabolic dysfunction-associated steatohepatitis

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 12, 2024

By replacing and removing defective or infected cells, programmed cell death (PCD) contributes to homeostasis maintenance body development, which is ubiquitously present in mammals can occur at any time. Besides apoptosis, more novel modalities of PCD have been described recently, such as necroptosis, pyroptosis, ferroptosis, autophagy-dependent death. not only regulates multiple physiological processes, but also participates the pathogenesis diverse disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD mainly classified into (MASL) steatohepatitis (MASH), latter putatively progresses cirrhosis hepatocellular carcinoma. Owing increased incidence obscure etiology MASH, its management still remains a tremendous challenge. Recently, hepatocyte has attracted much attention potent driver pathological progression from MASL some pharmacological agents proved exert their salutary effects on MASH partly via regulation activity PCD. The current review recapitulates different PCD, clarifies mechanisms underlying how disorders induce inflammatory fibrotic discusses several signaling pathways hepatocytes governing execution summarizes potential for treatment therapeutic These findings indicate that represents new point intervention MASH.

Language: Английский

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Curcumin induces autophagic cell death in human thyroid cancer cells

Toxicology in Vitro, Journal Year: 2021, Volume and Issue: 78, P. 105254 - 105254

Published: Oct. 9, 2021

Language: Английский

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Green Tea Epigallocatechin-3-Gallate Regulates Autophagy in Male and Female Reproductive Cancer

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: July 4, 2022

With a rich abundance of natural polyphenols, green tea has become one the most popular and healthiest nonalcoholic beverages being consumed worldwide. Epigallocatechin-3-gallate (EGCG) is predominant catechin found in tea, which been shown to promote numerous health benefits, including metabolic regulation, antioxidant, anti-inflammatory, anticancer. Clinical studies have also inhibitory effects EGCG on cancers male female reproductive system, ovarian, cervical, endometrial, breast, testicular, prostate cancers. Autophagy natural, self-degradation process that serves important functions both tumor suppression cell survival. Naturally derived products potential be an effective safe alternative balancing autophagy maintaining homeostasis during development. Although play critical role multiple cancers, its as modulator system remains fully discussed. Herein, we aim provide overview current knowledge targeting related signaling mechanism Effects regulating toward single therapy or cotreatment with other chemotherapies will reviewed compared. Additionally, underlying mechanisms crosstalk between cellular processes, such reactive oxidative stress, ER angiogenesis, apoptosis, summarized. The present review help shed light significance therapeutic treatment for through autophagy.

Language: Английский

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AAA237, an SKP2 inhibitor, suppresses glioblastoma by inducing BNIP3-dependent autophagy through the mTOR pathway

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 10, 2024

Abstract Background Glioblastoma (GBM) is the most common brain tumor with worst prognosis. Temozolomide only first-line drug for GBM. Unfortunately, resistance issue a classic problem. Therefore, it essential to develop new drugs treat As an oncogene, Skp2 involved in pathogenesis of various cancers including In this study, we investigated anticancer effect AAA237 on human glioblastoma cells and its underlying mechanism. Methods CCK-8 assay was conducted evaluate IC 50 values at 48, 72 h, respectively. The Cellular Thermal Shift Assay (CETSA) employed ascertain status as intrinsic target inside cellular milieu. EdU-DNA synthesis test, Soft-Agar Matrigel were performed check suppressive effects cell growth. To identify migration invasion ability GBM cells, transwell conducted. RT-qPCR Western Blot verify level BNIP3. mRFP-GFP-LC3 indicator system utilized assess alterations autophagy flux investigate impact dynamic fusion process between autophagosomes lysosomes. compound growth vivo, LN229 injected into brains mice orthotopic model. Results could inhibit vitro. bind expression degradation p21 p27. dose-dependent manner, demonstrated colony formation, migration, cells. treatment upregulate BNIP3 hub gene therefore induce BNIP3-dependent through mTOR pathway whereas 3-MA can somewhat reverse process. vivo , administration effectively suppressed development glioma tumors no side effects. Conclusion Compound AAA237, novel inhibitor, inhibited manner time-dependent upregulating induced might be viable therapeutic management Graphical

Language: Английский

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The Multifaceted Therapeutic Potential of Saffron: An Overview Based on Research and Patents

Drugs and Drug Candidates, Journal Year: 2024, Volume and Issue: 3(3), P. 437 - 454

Published: June 21, 2024

Plants and plant extracts have long been acknowledged as valuable resources for the development of therapeutic formulations various diseases. Among them, numerous plants plant-derived products demonstrated cytotoxic and/or anti-tumor properties. Saffron, particularly due to its major compounds, namely crocin, crocetin, safranal, stands out a promising candidate in this regard. Our research undertakes literature review, reaffirming antioxidant, anti-inflammatory, and, notably, properties saffron constituents. Additionally, study examines relevant patent documents, highlighting innovative applications compounds cancer therapy. The review discusses progress purifying extracted from assesses their impact on trial outcomes, potential synergies between certain established molecules, limitations patents examined, concerning reported clinical evidence. Researchers who focus advances oncology will know our findings evolution landscape regarding using or main compounds. Moreover, investigators can draw inspiration leveraging traditional knowledge, Chinese medicine, clarify specific active molecules mechanisms action expedite translation these into clinically interventions, potentially enhancing therapy outcomes.

Language: Английский

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RORA Regulates Autophagy in Hair Follicle Stem Cells by Upregulating the Expression Level of the Sqstm1 Gene

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 299 - 299

Published: Feb. 18, 2025

The hair coat is an adaptive evolutionary trait unique to mammals, aiding them in adapting complex environmental challenges. Although some of the factors involved regulating follicle development have been characterized, further in-depth research still needed. Retinoic acid receptor-related orphan receptor alpha (RORA), as a member nuclear family, highly regulation cellular states. Previous studies shown that autophagy plays significant role development. This study uses rat stem cells (HFSCs) model analyze impact RORA on levels HFSCs. Upon activation RORA, indicators such LC3-II/LC3-I ratio and MDC staining significantly increased, suggesting elevated level Following treatment with chloroquine, ratio, well expression BECN1 protein SQSTM1 protein, were markedly cells, indicating autophagic flux was unobstructed ruling out possibility impeded autophagy. Additionally, Sqstm1 gene increased after promoted cells. We found regulates transcription by binding its promoter region. believe promotes autophagy, particularly selective HFSCs, has potential become new target for provides theoretical foundation also offers insights diseases alopecia.

Language: Английский

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The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin

Molecules, Journal Year: 2021, Volume and Issue: 26(16), P. 4954 - 4954

Published: Aug. 16, 2021

Cordycepin is an adenosine derivative isolated from Cordyceps sinensis, which has been used as herbal complementary and alternative medicine with various biological activities. The general anti-cancer mechanisms of cordycepin are regulated by the A3 receptor, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), glycogen synthase kinase (GSK)-3β, leading to cell cycle arrest or apoptosis. Notably, also induces autophagy trigger death, inhibits tumor metastasis, modulates immune system. Since dysregulation associated cancers neuron, immune, kidney diseases, considered treatment because involvement in autophagic signaling. However, profound mechanism induction never reviewed detail. Therefore, this article, we health-promoting effects neurons, kidneys, system through diverse mechanisms, including induction. We suggest that formulation changes for could enhance its bioactivity bioavailability lower toxicity future applications. A comprehensive understanding would provide novel mechanistic insight into cordycepin.

Language: Английский

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Phloroglucinol Attenuates DNA Damage and Apoptosis Induced by Oxidative Stress in Human Retinal Pigment Epithelium ARPE-19 Cells by Blocking the Production of Mitochondrial ROS

Antioxidants, Journal Year: 2022, Volume and Issue: 11(12), P. 2353 - 2353

Published: Nov. 28, 2022

Phloroglucinol, a phenolic compound, is known to possess potent antioxidant ability. However, its role in retinal cells susceptible oxidative stress has not been well elucidated yet. Thus, the objective of this study was evaluate whether phloroglucinol could protect against damage cultured human pigment epithelium ARPE-19 cells. For purpose, were stimula ted with hydrogen peroxide (H2O2) mimic stress. Cell viability, cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, mitochondrial function, DNA damage, and autophagy then assessed. Our results revealed that ameliorated cell H2O2-exposued blocked production ROS. Phloroglucinol also counteracted H2O2-induced apoptosis by reducing Bax/Bcl-2 ratio, blocking activation caspase-3, inhibiting degradation poly (ADP-ribose) polymerase. H2O2 caused impairment increased expression levels mitophagy markers such as PINK1and PARKIN be associated ROS (mtROS) generation cytosolic release cytochrome c. these changes significantly attenuated phloroglucinol. Mito-TEMPO, selective antioxidant, further enhanced protective effect dysfunctional mitochondria. Furthermore, induced autophagy, but when pretreated phloroglucinol, meaning contributed pro-survival mechanism protected from autophagy. Taken together, suggest can inhibit stress-induced dysfunction protecting subsequent through mitigation mtROS generation. might have therapeutic potential prevent stress-mediated RPE

Language: Английский

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Modulators of Candida albicans Membrane Drug Transporters: A Lucrative Portfolio for the Development of Effective Antifungals

Molecular Biotechnology, Journal Year: 2024, Volume and Issue: 66(5), P. 960 - 974

Published: Jan. 11, 2024

Language: Английский

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