AGA induces sub-G1 cell cycle arrest and apoptosis in human colon cancer cells through p53-independent/p53-dependent pathway

BMC Cancer, Год журнала: 2023, Номер 23(1)

Опубликована: Янв. 2, 2023

Despite the advancement in chemotherapeutic drugs for colon cancer treatment, it is still a life-threatening disease worldwide due to drug resistance. Therefore, an urgently needed develop novel therapies. AGA combination of traditional Chinese medicine Antler's extract (A), Ganoderma lucidum (G), and Antrodia camphorata (A); contains lot biomolecules like polysaccharides, fatty acids, triterpenoids that are known exerting anti-oxidative, anti-inflammatory, anti-microbial anti-tumor activities oral cancer. In this study, we investigate anti-proliferative, anti-metastatic apoptotic activity explore its anti-cancer against cells underlying mechanism.Here, in-vitro studies were performed determine antiproliferative through MTT colony formation assays. Wound healing transwell migration assay used evaluate metastasis. Flow cytometry protein expression involved molecular mechanism by evaluating cell cycle apoptosis. The in-vivo anti-cancerous was assessed xenograft mice model cells.We found significantly inhibited proliferative capacity metastasis in-vitro. addition, induced arrest sub-G1 phase upregulating p21 downregulating CDK2, CDK6 SW620, CDK4 SW480 HT29, respectively. Annexin-v indicated had entered early late apoptosis after treatment with AGA. Furthermore, mechanistic expressions study revealed p53-dependent independent regulated p53 SW620 but dose-dependent manner HT29 increasing Bax caspase-9 inhibit cells. vivo reduced tumor growth NOD/SCID no adverse effect on kidney liver.Collectively, has potential inhibiting proliferation, migration, kinase promoting manner.

Язык: Английский

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A comprehensive review of computational cell cycle models in guiding cancer treatment strategies

npj Systems Biology and Applications, Год журнала: 2024, Номер 10(1)

Опубликована: Июль 5, 2024

Abstract This article reviews the current knowledge and recent advancements in computational modeling of cell cycle. It offers a comparative analysis various paradigms, highlighting their unique strengths, limitations, applications. Specifically, compares deterministic stochastic models, single-cell versus population mechanistic abstract models. detailed helps determine most suitable framework for research needs. Additionally, discussion extends to utilization these models illuminate cycle dynamics, with particular focus on viability, crosstalk signaling pathways, tumor microenvironment, DNA replication, repair mechanisms, underscoring critical roles progression optimization cancer therapies. By applying crucial aspects therapy planning better outcomes, including drug efficacy quantification, discovery, resistance analysis, dose optimization, review highlights significant potential insights enhancing precision effectiveness treatments. emphasis intricate relationship between therapeutic strategy development underscores pivotal role advanced techniques navigating complexities dynamics implications therapy.

Язык: Английский

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DRP1: At the Crossroads of Dysregulated Mitochondrial Dynamics and Altered Cell Signaling in Cancer Cells

ACS Omega, Год журнала: 2023, Номер 8(48), С. 45208 - 45223

Опубликована: Ноя. 17, 2023

In the past decade, compelling evidence has accumulated that highlights role of various subcellular structures in human disease conditions. Dysregulation these greatly impacts cellular function and, thereby, One such organelle extensively studied for its several diseases, especially cancer, is mitochondrion. DRP1 a GTPase considered master regulator mitochondrial fission and thereby also affects proper functioning organelle. Altered signaling pathways are distinguished characteristic cancer cells. this review, we aim to summarize our current understanding interesting crosstalk between structure–function maintained by affected We highlight structural aspects DRP1, regulation modifications, association protein with altered cancer. A better may help identifying potential pharmacological targets novel therapies

Язык: Английский

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Exploring therapeutic potential of Rutin by investigating its cyclin-dependent kinase 6 inhibitory activity and binding affinity

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 264, С. 130624 - 130624

Опубликована: Март 6, 2024

Язык: Английский

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Plant CDKs—Driving the Cell Cycle through Climate Change

Plants, Год журнала: 2021, Номер 10(9), С. 1804 - 1804

Опубликована: Авг. 30, 2021

In a growing population, producing enough food has become challenge in the face of dramatic increase climate change. Plants, during their evolution as sessile organisms, developed countless mechanisms to better adapt environment and its fluctuations. One important way is through plasticity body forms, which are modulated plant growth by accurate control cell divisions. A family serine/threonine kinases called cyclin-dependent (CDK) key regulator divisions controlling cycle progression. this review, we compile information on primary response plants regulation environmental stresses show how proteins (mainly kinases) involved can act components signaling cascades, triggering adaptive responses drive Understanding roles CDKs regulators adversity may be crucial meeting increasing agricultural productivity new climate.

Язык: Английский

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Mesenchymal Stem Cell-Derived Antimicrobial Peptides as Potential Anti-Neoplastic Agents: New Insight into Anticancer Mechanisms of Stem Cells and Exosomes

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Июль 6, 2022

Mesenchymal stem cells (MSCs), as adult multipotent cells, possess considerable regenerative and anti-neoplastic effects, from inducing apoptosis in the cancer to reducing multidrug resistance that bring them up an appropriate alternative for treatment. These can alter behavior of condition tumor microenvironment, activity immune result regression. It has been observed during inflammatory conditions, a well-known feature MSCs produce release some molecules called "antimicrobial peptides (AMPs)" with demonstrated effects. have remarkable targeted anticancer effects by attaching negatively charged membrane neoplastic disrupting membrane, interfering intracellular pathways. Therefore, AMPs could be considered part wide-ranging MSCs. This review focuses on possible MSCs-derived their mechanisms. also discusses preconditioning approaches using exosomes enhance AMP production delivery cells. Besides, clinical administration AMPs, along challenges practice, were debated.

Язык: Английский

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Neutrophil Extracellular Traps Upregulate p21 and Suppress Cell Cycle Progression to Impair Endothelial Regeneration after Inflammatory Lung Injury

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(5), С. 1204 - 1204

Опубликована: Фев. 20, 2024

Background: Sepsis is a major cause of ICU admissions, with high mortality and morbidity. The lungs are particularly vulnerable to infection injury, restoration vascular endothelial homeostasis after injury crucial determinant outcome. Neutrophil extracellular trap (NET) release strongly correlates the severity lung tissue damage. However, little known about whether NETs affect cell (EC) regeneration repair. Methods: Eight- ten-week-old male C57BL/6 mice were injected intraperitoneally sublethal dose LPS induce acute inflammatory or PBS as control. Blood samples tissues collected detect NET formation proliferation. Human umbilical vein cells (HUVECs) used determine role in cycle progression vitro. Results: Increased impaired proliferation observed following septic endotoxemia. Degradation DNase I attenuated inflammation facilitated regeneration. Mechanistically, induced p21 upregulation stasis impair Conclusions: Our findings suggest that impairs repair through induction arrest during injury.

Язык: Английский

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Ruthenium(II) Complex with 1-Hydroxy-9,10-Anthraquinone Inhibits Cell Cycle Progression at G0/G1 and Induces Apoptosis in Melanoma Cells

Pharmaceuticals, Год журнала: 2025, Номер 18(1), С. 63 - 63

Опубликована: Янв. 8, 2025

Melanoma is the most aggressive and lethal skin cancer that affects thousands of people worldwide. Ruthenium complexes have shown promising results as chemotherapeutics, offering several advantages over platinum drugs, such potent efficacy, low toxicity, less drug resistance. Additionally, anthraquinone derivatives broad therapeutic applications, including melanoma. Thus, two new ruthenium with 1-hydroxy-9,10-anthraquinone were obtained: trans-[Ru(HQ)(PPh3)2(bipy)]PF6 (1) cis-[RuCl2(HQ)(dppb)] (2), where HQ = 1-hydroxy-9,10-anthraquinone, PPh3 triphenylphospine, bipy 2,2'-bipyridine, PF6 hexafluorophosphate, dppb 1,4-bis(diphenylphosphine)butane. The characterized by infrared (IR), UV-vis, 1H, 13C{1H}, 31P{1H} NMR spectroscopies, molar conductivity, cyclic voltammetry, elemental analysis. Furthermore, density functional theory (DFT) calculations performed. Compound (2) was determined single-crystal X-ray diffraction, which confirms bidentate coordination mode through carbonyl phenolate oxygens. DNA-binding experiments yielded constants 105 M-1 (Kb 6.93 × for 1.60 (2)) demonstrate both can interact DNA intercalation, electrostatic attraction, or hydrogen bonding. cytotoxicity profiles compounds evaluated in human melanoma cell lines (SK-MEL-147, CHL-1, WM1366), revealing greater cytotoxic activity on CHL-1 line an IC50 14.50 ± 1.09 µM. Subsequent studies showed inhibits proliferation cells induces apoptosis, associated at least part pro-oxidant effect cycle arrest G1/S transition.

Язык: Английский

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TET2-mediated 5-hydroxymethylcytosine of TXNIP promotes cell cycle arrest in systemic anaplastic large cell lymphoma

Clinical Epigenetics, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 21, 2025

5-Hydroxymethylcytosine (5hmC) modification represents a significant epigenetic within DNA, playing pivotal role in range of biological processes associated with various types cancer. The 5hmC systemic anaplastic large cell lymphoma (ALCL) has not been thoroughly investigated. This study aims to examine the function advancement ALCL. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues (n = 46) were obtained from ALCL patients. GEO dataset was used analyze expression 5hmC-relative enzymes. Immunohistochemistry conducted assess level and Ten-eleven translocation 2 (TET2) on FFPE samples. ALK-positive line, Su-DHL-1, ALK-negative DL-40, utilized as vitro experimental models. RNA-sequencing hMeDIP-sequencing assays performed explore potential functions TET2 cycle regulation. Our identified reduction levels patients ALCL, which exhibited positive correlation expression. Downregulation resulted decreased facilitated progression lines. hMeDIP-seq subsequent functional analyses demonstrated involvement thioredoxin interacting protein (TXNIP) regulation cells. Further mechanistic studies revealed that influenced TXNIP underscores roles Therapeutic strategies aimed at targeting or may offer novel approach for management

Язык: Английский

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Loss of Cochlin drives impairments in tendon structure and function

Matrix Biology Plus, Год журнала: 2025, Номер 25, С. 100168 - 100168

Опубликована: Фев. 1, 2025

Язык: Английский

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