Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond

World Journal of Gastroenterology, Год журнала: 2023, Номер 29(9), С. 1395 - 1426

Опубликована: Март 7, 2023

Colorectal cancer (CRC) is the third most diagnosed malignancy and a major leading cause of cancer-related deaths worldwide. Despite advances in therapeutic regimens, number patients presenting with metastatic CRC (mCRC) increasing due to resistance therapy, conferred by small population cells, known as stem cells. Targeted therapies have been highly successful prolonging overall survival mCRC. Agents are being developed target key molecules involved drug-resistance metastasis CRC, these include vascular endothelial growth factor, epidermal factor receptor, human receptor-2, mitogen-activated extracellular signal-regulated kinase, addition immune checkpoints. Currently, there several ongoing clinical trials newly targeted agents, which shown considerable efficacy improved prognosis who do not benefit from conventional chemotherapy. In this review, we highlight recent developments use existing novel agents against drug-resistant Furthermore, discuss limitations challenges associated therapy strategies combat intrinsic acquired therapies, importance implementing better preclinical models application personalized based on predictive biomarkers for treatment selection.

Язык: Английский

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The role of Nrf2 in the pathogenesis and treatment of ulcerative colitis

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Июнь 5, 2023

Ulcerative colitis (UC) is a chronic inflammatory bowel disease involving mainly the colorectal mucosa and submucosa, incidence of which has been on rise in recent years. Nuclear factor erythroid 2-related 2 (Nrf2), known for its key function as transcription factor, pivotal inducing antioxidant stress regulating responses. Numerous investigations have demonstrated involvement Nrf2 pathway maintaining development normal intestine, UC, UC-related intestinal fibrosis carcinogenesis; meanwhile, therapeutic agents targeting widely investigated. This paper reviews research progress signaling UC.

Язык: Английский

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Lactobacillus rhamnosus GG cell-free supernatant as a novel anti-cancer adjuvant

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Март 14, 2023

Abstract Background Gut microbiota modulation has been demonstrated to be effective in protecting patients against detrimental effects of anti-cancer therapies, as well improve the efficacy certain treatments. Among most characterized probiotics, Lactobacillus rhamnosus GG (LGG) is currently utilized clinics alleviate diarrhea, mucositis or intestinal damage which might associated with several triggers, including Clostridium difficile infections, inflammatory gut diseases, antibiotic consumption, chemotherapy radiation therapy. Here, we investigate whether LGG cell-free supernatant (LGG-SN) exert anti-proliferative activity toward colon cancer and metastatic melanoma cells. Moreover, assess potential adjuvant effect LGG-SN combination drugs. Methods alone either 5-Fuorouracil Irinotecan was used treat human cell lines. Dimethylimidazol-diphenyl tetrazolium bromide assay employed detect cellular viability. Trypan blue staining, anti-cleaved caspase-3 anti-total versus PARP western blots, annexin V/propidium iodide flow cytometry analyses were death. Flow measurement DNA content (with propidium staining) together qPCR analysis cyclins expression cycle. Results We demonstrate that able selectively reduce viability cells a concentration-dependent way. While does not any on control fibroblasts. In cells, reduction apoptosis induction, but mitotic arrest G2/M phase Additionally, sensitizes both 5-Fluorouracil Irinotecan, thereby showing positive synergistic action. Conclusion Overall, our results suggest may contain one more bioactive molecules sensitize chemotherapeutic Thus, could proposed an ideal candidate for ground-breaking integrated approaches oncology, chemotherapy-related side overcome resistance relapse issues, thus ameliorating therapeutic response patients.

Язык: Английский

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Resveratrol as sensitizer in colorectal cancer plasticity

Cancer and Metastasis Reviews, Год журнала: 2023, Номер 43(1), С. 55 - 85

Опубликована: Июль 29, 2023

Abstract Despite tremendous medical treatment successes, colorectal cancer (CRC) remains a leading cause of deaths worldwide. Chemotherapy as monotherapy can lead to significant side effects and chemoresistance that be linked several resistance-activating biological processes, including an increase in inflammation, cellular plasticity, multidrug resistance (MDR), inhibition the sentinel gene p53, apoptosis. As consequence, tumor cells escape effectiveness chemotherapeutic agents. This underscores need for cross-target therapeutic approaches are not only pharmacologically safe but also modulate multiple potent signaling pathways sensitize overcome standard drugs. In recent years, scientists have been searching natural compounds used chemosensitizers addition conventional medications synergistic CRC. Resveratrol, polyphenolic phytoalexin found various fruits vegetables such peanuts, berries, red grapes, is one most effective chemopreventive Abundant vitro vivo studies shown resveratrol, interaction with drugs, chemosensitizer CRC agents thus prevents drug by modulating pathways, transcription factors, epithelial-to-mesenchymal transition-plasticity, proliferation, metastasis, angiogenesis, cell cycle, The ability resveratrol modify subcellular may suppress plasticity reversal critical parameters understanding its anti-cancer effects. this review, we focus on chemosensitizing properties and, thus, potential importance additive ongoing treatments. Graphical abstract

Язык: Английский

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Interaction of 5-Fluorouracil on the Surfaces of Pristine and Functionalized Ca₁₂O₁₂ Nanocages: An Intuition from DFT

ACS Omega, Год журнала: 2023, Номер 8(15), С. 13551 - 13568

Опубликована: Апрель 3, 2023

The utilization of nanostructured materials for several biomedical applications has tremendously increased over the last few decades owing to their nanosizes, porosity, large surface area, sensitivity, and efficiency as drug delivery systems. Thus, incorporation functionalized pristine nanostructures cancer therapy offers substantial prospects curb persistent problems ineffective administration target sites. potential (Ca12O12) formyl (-CHO)- amino (-NH2)-functionalized (Ca12O12-CHO Ca12O12-NH2) derivatives efficient nanocarriers 5-fluorouracil (5FU) was studied at B3LYP-GD3(BJ)/6-311++G(d,p) theoretical level in two electronic media (gas solvent). To effectively account all adsorption interactions on investigated surfaces, studies well topological analysis based quantum theory atoms molecules (QTAIM) noncovalent were exhaustively utilized. Interestingly, obtained results divulged that 5FU interacted favorably with both Ca12O12 its derivatives. energies calculated be -133.4, -96.9, -175.6 kcal/mol, respectively, Ca12O12, Ca12O12-CHO, Ca12O12-NH2. Also, NBO stabilization revealed presence among O3-H32, O27-C24, O10-C27, N24-H32 surface. However, 5FU@Ca12O12-CHO portrayed least energy due considerable destabilization molecular complex by computed deformation energy. Therefore, 5FU@Ca12O12 5FU@Ca12O12-NH2 acted better nanovehicles 5FU.

Язык: Английский

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c-Fos regulated by TMPO/ERK axis promotes 5-FU resistance via inducing NANOG transcription in colon cancer

Cell Death and Disease, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 17, 2024

Abstract Acquired drug resistance is one of the most common limitations for clinical response colon cancer to 5-Fluorouracil (5-FU)-based chemotherapy. The relevant molecular mechanisms might be diversity, but still not elucidated clearly. In this study, we aimed investigate potential c-Fos, a subfamily activator protein-1, in 5-FU chemoresistance. We determined that phosphorylated c-Fos promoted cells by facilitating stemness. Mechanically, treatment induced autolysosome-dependent degradation TMPO, which subsequently triggered ERK-mediated phosphorylation c-Fos. Additionally, was found bind promoter NANOG and at Ser 374 required its regulation expression. ablation impaired c-Fos/p-c-Fos Taken together, these findings revealed TMPO-mediated conferred regulating expression promoting cell stemness cells. could as therapeutic target cancer.

Язык: Английский

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Isolation, structural characterization and biological activity evaluation of melanoidins from thermally processed cocoa beans, carob kibbles and acorns as potential cytotoxic agents

Food Chemistry, Год журнала: 2024, Номер 442, С. 138423 - 138423

Опубликована: Янв. 21, 2024

Язык: Английский

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Advancements in 5-fluorouracil-Loaded liposomal nanosystems: A comprehensive review on recent innovations in nanomedicine for cancer therapy

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 96, С. 105730 - 105730

Опубликована: Апрель 28, 2024

Язык: Английский

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Flavonoids and Gastric Cancer Therapy: From Signaling Pathway to Therapeutic Significance

Drug Design Development and Therapy, Год журнала: 2024, Номер Volume 18, С. 3233 - 3253

Опубликована: Июль 1, 2024

Gastric cancer (GC) is a prevalent gastrointestinal tumor characterized by high mortality and recurrence rates. Current treatments often have limitations, prompting researchers to explore novel anti-tumor substances develop new drugs. Flavonoids, natural compounds with diverse biological activities, are gaining increasing attention in this regard. We searched from PubMed, Web of Science, SpringerLink other databases find the relevant literature last two decades. Using "gastric cancer", "stomach cancers", "flavonoid", "bioflavonoid", "2-Phenyl-Chromene" as keywords, were searched, then analyzed summarized mechanism flavonoids treatment GC. It was revealed that involves inhibiting growth, proliferation, invasion, metastasis, well inducing cell death through various processes such apoptosis, autophagy, ferroptosis, pyroptosis. Additionally, combining chemotherapeutic agents like 5-FU platinum can potentially reduce chemoresistance. Flavonoids also demonstrated enhanced activity when used combination products. Consequently, review proposes innovative perspectives for development anti-GC agents.

Язык: Английский

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From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9463 - 9463

Опубликована: Авг. 30, 2024

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance treatment approaches. This article provides comprehensive review our current understanding CRC epidemiology, risk factors, pathogenesis, management strategies. We also present intricate cellular architecture colonic crypts their roles intestinal homeostasis. carcinogenesis multistep processes are described, covering conventional adenoma-carcinoma sequence, alternative serrated pathways, influential Vogelstein model, which proposes sequential

Язык: Английский

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