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Targeting the two-pore channel 2 in cancer progression and metastasis.

The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions

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… Wong VKW Zeng W Chen J Yao XJ Leung ELH Wang QQ Tetrandrine, an activator of autophagy, induces autophagic cell death via PKC-α inhibition and mTOR-dependent mechanisms . Front Pharmacol . 2017 ; 8 : 351 . 10.3389/fphar.2017.00351 28642707 PMC5462963 156. Wang CH Yang JM Guo YB Shen J Pei XH. …

Потенциальные цели микроглии в лечении нейродегенеративных заболеваний: механизм и терапевтические последствия.

В случае различных нейродегенеративных расстройств активируются микроглиальные клетки. Кроме того, дисфункциональная и гиперактивированная микроглия инициирует митохондриальную автофагию, окислительный стресс и патологическое накопление белка, заканчивающееся нейроинфламмацией, которая усугубляет повреждения допаминергических нейронов и вносит значительный вклад в патологию нейродегенеративного расстройства. Микроглиальная чрезмерная активация тесно связана с секрецией провоспалительных цитокинов, фагоцитозом травмированных нейронов и модуляцией нейротоксичной среды. В этом обзоре резюмируется

Protein breakdown in muscle wasting: role of autophagy-lysosome and ubiquitin-proteasome.

Skeletal muscle adapts its mass as consequence of physical activity, metabolism and hormones. Catabolic conditions or inactivity induce signaling pathways that regulate the process of muscle loss. Muscle atrophy in adult tissue occurs when protein degradation rates exceed protein synthesis. Two major protein degradation pathways, the ubiquitin-proteasome and the autophagy-lysosome systems, are activated during muscle atrophy and variably contribute to the loss of muscle mass. These degradation systems are controlled by a transcription dependent program that modulates the expression of rate-lim

Marine-Derived Compounds: A New Horizon in Cancer, Renal, and Metabolic Disease Therapeutics.

Marine-derived compounds represent a rich source of structurally diverse molecules with therapeutic potential for cancer, renal disorders, metabolic-associated fatty liver disease (MAFLD), and atherosclerosis. This review systematically evaluates recent advances, highlighting compounds such as Microcolin H, Benzosceptrin C, S14, HN-001, Equisetin, glycosides (e.g., cucumarioside A2-2), ilimaquinone, and Aplidin (plitidepsin). Key mechanisms include autophagy modulation, immune checkpoint inhibition, anti-inflammatory effects, and mitochondrial homeostasis. Novel findings reveal glycosides' dua

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… By binding to PITPα/β, it inhibits cancer cell proliferation and migration, and induces autophagic cell death, as evidenced by increased LC3II conversion and decreased p62 levels. … Mechanistic studies and target validation showed that chemical proteomics identified phosphatidylinositol transfer proteins PITPα/β as direct binding targets of Microcolin H (KD = 6.2 μM, MST analysis [ 7 ]), through which it induced autophagic cell death. …

Recent Advances in Understanding the Mechanisms of Elemene in Reversing Drug Resistance in Tumor Cells: A Review.

Malignant tumors are life-threatening, and chemotherapy is one of the common treatment methods. However, there are often many factors that contribute to the failure of chemotherapy. The multidrug resistance of cancer cells during chemotherapy has been reported, since tumor cells' sensitivity decreases over time. To overcome these problems, extensive studies have been conducted to reverse drug resistance in tumor cells. Elemene, an extract of the natural drug Curcuma wenyujin, has been found to reverse drug resistance and sensitize cancer cells to chemotherapy. Mechanisms by which elemene rever

The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms.

The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The in

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… An interesting study demonstrated the potential of silibinin to induce autophagic cell death in breast cancer cells. This effect was confirmed by high expression of LC3-II, increase of Beclin-1, high Atg-12-Atg-5, and down-regulation of Bcl-2 [ 132 ]. …

Диметилфумарат уменьшает травму от печени ишемии и реперуляции путем подавления сигнала CGAS-STING.

Повреждение печени во время периоперационной фазы операции на печени часто происходит в результате печени. Неправильная активация сигнала СТИНГ может вызвать чрезмерную воспламенение реакции на усугубление печени. Диметилфумарат (DMF) — разрешенный УЛХ иммунодулятор, используемый для лечения множественного склероза и псориаза в силу его заметных свойств против воспаления. Однако механизм и целевые показатели ДМФ в области иммуномодуляции остаются неясными. Здесь мы обнаружили, что DMF подавляет активацию CGAS-STING, индуцируемую HSV-1, ДНК яичек и митохондриальная ДНК в различных клетках. DMF

Deciphering the impact of circRNA-mediated autophagy on tumor therapeutic resistance: a novel perspective.

Cancer therapeutic resistance remains a significant challenge in the pursuit of effective treatment strategies. Circular RNAs (circRNAs), a class of non-coding RNAs, have recently emerged as key regulators of various biological processes, including cancer progression and drug resistance. This review highlights the emerging role of circRNAs-mediated autophagy in cancer therapeutic resistance, a cellular process that plays a dual role in cancer by promoting both cell survival and death. Increasing evidence suggests that circRNAs can modulate autophagy pathways, thereby influencing the response o

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… Conversely, mTOR activation can facilitate autophagic cell death, increasing γ-ray cytotoxicity in EGFR mutant non-small cell lung cancer (NSCLC) [ 62 ]. Inactivation of the AKT/p70S6K pathway releases autophagy repression, promoting γ-radiation sensitivity in malignant glioma cells [ 63 ]. … Tsuboi Y Kurimoto M Nagai S Hayakawa Y Kamiyama H Hayashi N Kitajima I Endo S Induction of autophagic cell death and radiosensitization by the pharmacological inhibition of nuclear factor-kappa B activation in human glioma cell lines J Neurosurg 2009 110 594 604 10.3171/2008.8.JNS17648 19046042 75. …

Cancer Stem Cells: The Potential Targets of Chinese Medicines and Their Active Compounds.

The pivotal role of cancer stem cells (CSCs) in the initiation and progression of malignancies has been rigorously validated, and the specific methods for identifying and isolating the CSCs from the parental cancer population have also been rapidly developed in recent years. This review aims to provide an overview of recent research progress of Chinese medicines (CMs) and their active compounds in inhibiting tumor progression by targeting CSCs. A great deal of CMs and their active compounds, such as Antrodia camphorate, berberine, resveratrol, and curcumin have been shown to regress CSCs, in t

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… Signaling Pathways Involved in Regulating Proliferation and Cell Death in CSCs Evasion from apoptotic or autophagic cell death and unlimited proliferation are another major characteristic of CSCs ( Figure 2 ). … Autophagic cell death also plays an important role in regulating chemoradiation resistance, self-renewal and differentiation in CSCs. Bcl-2/Bcl-XL signaling pathway is related to the regulation of autophagic cell death in CSCs. …

Natural Products as Anticancer Agents: Current Status and Future Perspectives.

Natural products have been an invaluable and useful source of anticancer agents over the years. Several compounds have been synthesized from natural products by modifying their structures or by using naturally occurring compounds as building blocks in the synthesis of these compounds for various purposes in different fields, such as biology, medicine, and engineering. Multiple modern and costly treatments have been applied to combat cancer and limit its lethality, but the results are not significantly refreshing. Natural products, which are a significant source of new therapeutic drugs, are cu

Screening the Active Phytochemicals From Eclipta prostrata and Unraveling Their Molecular Insight Into Human Malignancies.

Current drugs against multiple human malignancies are limited, and developing new treatment strategies is improbable within a short time. So, considering the current situation, phytochemicals could be a viable option for developing chemotherapeutic agents for managing numerous types of malignancies. Therefore, we aimed to locate all phytochemicals of Eclipta prostrata and unravel their chemotherapeutic mechanisms and strategies individually. We defined 25 active compounds based on their anticancer activities after filtering through IMPPAT and literature search, and these compounds have chemoth

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… The compound induces both apoptotic and autophagic cell death in SKOV3 and A2780 ovarian carcinoma cells, as evidenced by Annexin V staining and increased acidic vesicular organelle content. …

Molecular and cellular mechanisms of skeletal muscle atrophy: an update.

Skeletal muscle atrophy is defined as a decrease in muscle mass and it occurs when protein degradation exceeds protein synthesis. Potential triggers of muscle wasting are long-term immobilization, malnutrition, severe burns, aging as well as various serious and often chronic diseases, such as chronic heart failure, obstructive lung disease, renal failure, AIDS, sepsis, immune disorders, cancer, and dystrophies. Interestingly, a cooperation between several pathophysiological factors, including inappropriately adapted anabolic (e.g., growth hormone, insulin-like growth factor 1) and catabolic pr

MicroRNA-7: a versatile player and core target in brain disorders.

OBJECTIVE: This article provides a systematic review of the biological characteristics, regulatory mechanisms, and roles of MicroRNA-7 (miR-7) in the nervous system, as well as explores its clinical translation potential and challenges. METHODS: A review analysis integrating the progress of basic and clinical research related to miR-7. RESULTS: Characteristics and Regulation: miR-7 is highly expressed in mammalian brain tissues, with its function finely regulated by ceRNA networks (such as ciRS-7 and lncRNA SNHG1) and epigenetic modifications, forming a multi-layer dynamic regulatory system.

Statins: a repurposed drug to fight cancer.

As competitive HMG-CoA reductase (HMGCR) inhibitors, statins not only reduce cholesterol and improve cardiovascular risk, but also exhibit pleiotropic effects that are independent of their lipid-lowering effects. Among them, the anti-cancer properties of statins have attracted much attention and indicated the potential of statins as repurposed drugs for the treatment of cancer. A large number of clinical and epidemiological studies have described the anticancer properties of statins, but the evidence for anticancer effectiveness of statins is inconsistent. It may be that certain molecular subt

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… When autophagy is insufficient to reduce stress and compensate for cellular damage, this results in autophagic cell death, which is similar to apoptosis [ 223 , 224 ]. … The combination of lovastatin and cisplatin has been found to enhance expression of the autophagy marker LC3B-II and decrease the viability of cancer cells through the induction of autophagic cell death [ 244 ]. …

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.

Metastatic dissemination of solid tumors, a leading cause of cancer-related mortality, underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis, chemoresistance, and the mechanistic backgrounds of individuals whose cancers are prone to migration. The most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase (MAPK) pathway, encompassing the RAS-RAF-MAPK kinase (MEK)-extracellular signal-related kinase (ERK) pathway. RAF kinase is a primary mediator of the MAPK pathway, responsible for th

Targeting the AMP-Activated Protein Kinase for Cancer Prevention and Therapy.

Despite the advances in biomedical research and clinical applications, cancer remains a leading cause of death worldwide. Given the limitations of conventional chemotherapeutics, including serious toxicities and reduced quality of life for patients, the development of safe and efficacious alternatives with known mechanism of action is much needed. Prevention of cancer through dietary intervention may hold promise and has been investigated extensively in the recent years. AMP-activated protein kinase (AMPK) is an energy sensor that plays a key role in the regulation of protein and lipid metabol

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… Under certain circumstances, autophagic cells may engage a specific mode of cell death called type II cell death or autophagic cell death (ACD). A number of studies have revealed the role of AMPK in ACD of cancer cells ( 38 , 39 ). … Int J Cancer ( 2012 ) 130 : 1695 – 705 10.1002/ijc.26178 21618507 PMC3267899 87 Suh Y Afaq F Khan N Johnson JJ Khusro FH Mukhtar H Fisetin induces autophagic cell death through suppression of mTOR signaling pathway in prostate cancer cells . …

From bench to bedside: the application of cannabidiol in glioma.

Glioma is the most common malignant tumor in central nervous system, with significant health burdens to patients. Due to the intrinsic characteristics of glioma and the lack of breakthroughs in treatment modalities, the prognosis for most patients remains poor. This results in a heavy psychological and financial load worldwide. In recent years, cannabidiol (CBD) has garnered widespread attention and research due to its anti-tumoral, anti-inflammatory, and neuroprotective properties. This review comprehensively summarizes the preclinical and clinical research on the use of CBD in glioma therapy

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… Huang and others found that CBD activates the TRPV4, causing extracellular calcium influx that induces ER stress and mitochondrial autophagy in glioma cells through ATF4-DDIT3-TRIB3-AKT-mTOR axis, ultimately leading to lethal autophagic cell death [ 28 ]. …

Drug Repurposing of Selected Antibiotics: An Emerging Approach in Cancer Drug Discovery.

Drug repurposing is a method of investigating new therapeutic applications for previously approved medications. This repurposing approach to "old" medications is now highly efficient, simple to arrange, and cost-effective and poses little risk of failure in treating a variety of disorders, including cancer. Drug repurposing for cancer therapy is currently a key topic of study. It is a way of exploring recent therapeutic applications for already-existing drugs. Theoretically, the repurposing strategy has various advantages over the recognized challenges of creating new molecular entities, inclu

Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran.

Gastrointestinal cancers are a major global health challenge, with high mortality rates. This study investigated the anti-cancer activities of 30 monomers extracted from Morus alba L. (mulberry) against gastrointestinal cancers. Toxicological assessments revealed that most of the compounds, particularly immunotoxicity, exhibit some level of toxicity, but it is generally not life-threatening under normal conditions. Among these components, Sanggenol L, Sanggenon C, Kuwanon H, 3'-Geranyl-3-prenyl-5,7,2',4'-tetrahydroxyflavone, Morusinol, Mulberrin, Moracin P, Kuwanon E, and Kuwanon A demonstrate

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… Oxyresveratrol activates parallel apoptotic and autophagic cell death pathways in neuroblastoma cells. Biochim. Biophys. Acta Gen. Subj. 2017;1861:23–36. doi: 10.1016/j.bbagen.2016.10.025. 94. Amorntaveechai A., Osathanon T., Pavasant P., Sooampon S. …

Nostoc commune-derived scytonemin induced mitochondrial cell death in leukemia models.

Cyanobacteria have long attracted scientific interest through their potential application in the development of new therapeutic approaches, particularly those related to the treatment of cancer. In this study, the antiproliferative effects of Nostoc commune extract (NOS) and the cyanobacterial compound scytonemin (SCY) were evaluated against a variety of in vitro cancer models, including cervix, colon, breast, lung, and leukemia cell lines, using resazurin assays. Both of the studied compounds were found to have inhibited metabolic activity in a dose-dependent manner, with IC50 values ranging

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… A reduced form of scytonemin, isolated from the cyanobacterium Nostoc commune , had an inhibitory effect on the growth of acute leukemia Jurkat cells by inducing autophagic cell death. … Reduced scytonemin isolated from Nostoc commune induces autophagic cell death in human T-lymphoid cell line Jurkat cells. Food Chem Toxicol. 2013;60:76–82. 10.1016/j.fct.2013.07.016. 13. Rastogi RP, Incharoensakdi A. …