Natural Alternatives in the Treatment of Colorectal Cancer: A Mechanisms Perspective DOI Creative Commons
Karen Vanessa Fernandez-Muñoz, Ángel Sánchez‐Barrera, Marco Antonio Meraz‐Ríos

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 326 - 326

Published: Feb. 24, 2025

Colorectal cancer (CRC) is one of the deadliest neoplasia. Intrinsic or acquired resistance main cause failure therapy regimens that leads to relapse and death in CRC patients. The widely used chemotherapeutic agent 5-fluorouracil (5-FU) remains mainstay for therapeutic combinations. Unfortunately, side effects are frequent events compromise success these therapies; dysregulation enzymes regulate 5-FU metabolism increases expression activity efflux pumps. Additional tumor cell adaptations such as epithelial–mesenchymal transition (EMT), autophagy shaping microenvironment, inflammation contribute chemoresistance. Finding new strategies alternatives enhance conventional chemotherapies has become necessary. Recently, study natural compounds been gaining strength an alternative chemotherapeutics different cancers. Curcumin, trimethylglycine, resveratrol, artemisinin, some helminth-derived molecules, among others, studied context CRC. This review discusses benefits, mechanisms, advances, dark currently evaluated treatment. We also analyzed landscape non-conventional their underlying mechanisms action, which could, short term, provide fundamental knowledge harness anti-tumor allow them be adjuvant therapies.

Language: Английский

5‐Fluorouracil resistance mechanisms in colorectal cancer: From classical pathways to promising processes DOI Creative Commons

Sabrina Blondy,

Valentin David, Mireille Verdier

et al.

Cancer Science, Journal Year: 2020, Volume and Issue: 111(9), P. 3142 - 3154

Published: June 14, 2020

Abstract Colorectal cancer (CRC) is a public health problem. It the third most common in world, with nearly 1.8 million new cases diagnosed 2018. The only curative treatment surgery, especially for early tumor stages. When there locoregional or distant invasion, chemotherapy can be introduced, particular 5‐fluorouracil (5‐FU). However, disease become tolerant to these pharmaceutical treatments: resistance emerges, leading recurrence. Different mechanisms explain this 5‐FU resistance. Some are disease‐specific, whereas others, such as drug efflux, evolutionarily conserved. These numerous and complex occur simultaneously cells exposed 5‐FU. In review, we construct global outline of different from disruption 5‐FU‐metabolic enzymes classic cellular processes (apoptosis, autophagy, glucose metabolism, oxidative stress, respiration, cell cycle perturbation) transporters epithelial‐mesenchymal transition induction. Particular interest directed microenvironment function well epigenetic alterations miRNA dysregulation, which more promising that will subject much research future.

Language: Английский

Citations

380
Novel therapeutic strategies: targeting epithelial–mesenchymal transition in colorectal cancer DOI
Nan Zhang, Aik Seng Ng, Shijie Cai

et al.

The Lancet Oncology, Journal Year: 2021, Volume and Issue: 22(8), P. e358 - e368

Published: July 30, 2021

Language: Английский

Citations

244
Drug Resistance in Colorectal Cancer: From Mechanism to Clinic DOI Open Access
Qianyu Wang, Xiaofei Shen, Gang Chen

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(12), P. 2928 - 2928

Published: June 14, 2022

Colorectal cancer (CRC) is one of the leading causes death worldwide. The 5-year survival rate 90% for patients with early CRC, 70% locally advanced and 15% metastatic CRC (mCRC). In fact, most are at an stage time diagnosis. Although chemotherapy, molecularly targeted therapy immunotherapy have significantly improved patient survival, some initially insensitive to these drugs or sensitive but quickly become insensitive, emergence such primary secondary drug resistance a significant clinical challenge. direct cause aberrant anti-tumor metabolism, transportation target. With more in-depth research, it found that cell pathways, carcinogenic signals, compensation feedback loop signal pathways tumor immune microenvironment also play essential roles in mechanism. Here, we assess current major mechanisms describe potential therapeutic interventions.

Language: Английский

Citations

84
Kaempferol Can Reverse the 5-Fu Resistance of Colorectal Cancer Cells by Inhibiting PKM2-Mediated Glycolysis DOI Open Access
Haili Wu,

Jin’e Du,

Chenglu Li

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3544 - 3544

Published: March 24, 2022

Resistance to 5-Fluorouracil (5-Fu) chemotherapy is the main cause of treatment failure in cure colon cancer. Therefore, there an urgent need explore a safe and effective multidrug resistance reversal agent for colorectal cancer, which would be great significance improving clinical efficacy. The dietary flavonoid kaempferol plays key role progression cancer 5-Fu resistance. However, molecular mechanism reversing human cells still unclear. We found that could reverse drug HCT8-R 5-Fu, suggesting alone or combination with has potential treat It well known aerobic glycolysis related tumor growth Indeed, significantly reduced glucose uptake lactic acid production drug-resistant cells. In terms mechanism, promotes expression microRNA-326 (miR-326) cells, miR-326 inhibit process by directly targeting pyruvate kinase M2 isoform (PKM2) 3'-UTR (untranslated region) PKM2 indirectly block alternative splicing factors PKM mRNA, then 5-Fu. Taken together, our data suggest may play important overcoming therapy regulating miR-326-hnRNPA1/A2/PTBP1-PKM2 axis.

Language: Английский

Citations

76
Plant Foods and Their Bioactives as Dietary Enhancers for Colon Cancer Treatment with 5-Fluorouracil DOI
Zhongming Yang, Carlos L. Céspedes, Zhongguo Yang

et al.

Food Reviews International, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 50

Published: Jan. 4, 2025

Cancer is the world's second most common cause of death, with colon cancer (CC) ranking third in prevalence and cancer-related fatalities. CC originates or rectum influenced by genetic mutations, lifestyle, diet. Although chemotherapy, especially 5-fluorouracil (5-FU), fundamental to treatment has improved patient survival, its benefits are often limited significant side effects emerging drug resistance. Recently, plant-based foods have drawn interest research for their natural bioactive compounds relatively low toxicity. Certain plant not only exhibit anti-cancer activity but may also boost effectiveness 5-FU while reducing adverse effects. Despite evidence suggesting a synergistic effect between 5-FU, this area remains fragmented. This review consolidates current on including fruits, vegetables, legumes, tea bioactives treatment. Besides, it explores mechanisms through which these enhance efficacy reduce effects, evaluates clinical application prospects, identifies challenges future directions. comprehensive analysis aims provide scientific foundation integrated CC, highlighting potential enhancing chemotherapy associated toxicities.

Language: Английский

Citations

6
New insights into natural products that target the gut microbiota: Effects on the prevention and treatment of colorectal cancer DOI Creative Commons
Lu Lu,

Jiahuan Dong,

Yujing Liu

et al.

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

Published: Aug. 15, 2022

Colorectal cancer (CRC) is one of the most common malignant carcinomas. CRC characterized by asymptomatic onset, and patients are already in middle advanced stages disease when they diagnosed. Inflammatory bowel (IBD) inflammatory-cancer transformation colorectal adenoma main causes CRC. There an urgent need for effective prevention intervention strategies In recent years, rapid research progress has increased our understanding gut microbiota. Meanwhile, with deepening on pathogenesis cancer, microbiota been confirmed to play a direct role occurrence treatment cancer. Strategies regulate have potential value application Regulation important ways natural products exert pharmacological effects, especially metabolic diseases tumours. This review summarizes tumorigenesis mechanism which reduce improve therapeutic response. We point out that regulation may serve as means

Language: Английский

Citations

63
The POU2F1-ALDOA axis promotes the proliferation and chemoresistance of colon cancer cells by enhancing glycolysis and the pentose phosphate pathway activity DOI Creative Commons

Jinguan Lin,

Longzheng Xia,

Linda Oyang

et al.

Oncogene, Journal Year: 2022, Volume and Issue: 41(7), P. 1024 - 1039

Published: Jan. 8, 2022

Abstract Cancer metabolic reprogramming enhances its malignant behaviors and drug resistance, which is regulated by POU domain transcription factors. This study explored the effect of class 2 factor 1 (POU2F1) on in colon cancer. The POU2F1 expression was analyzed GEO dataset, TCGA cohorts human cancer tissues bioinformatics immunohistochemistry. effects altered proliferation, glucose metabolism oxaliplatin sensitivity cells were tested. impacts aldolase A (ALDOA) examined. We found that up-regulated associated with worse prognosis resistance enhanced aerobic glycolysis pentose phosphate pathway (PPP) activity, but reduced oxidative stress apoptosis cells, dependent up-regulating ALDOA expression. Mechanistically, directly bound to promoter enhance activity cells. Moreover, activation POU2F1-ALDOA axis decreased These data indicate promotes progression enhancing Our findings suggest may be new therapeutic targets overcome

Language: Английский

Citations

61
Targeting the miR-34a/LRPPRC/MDR1 axis collapse the chemoresistance in P53 inactive colorectal cancer DOI Open Access
Yang Yang,

Hongyu Yuan,

Lianmei Zhao

et al.

Cell Death and Differentiation, Journal Year: 2022, Volume and Issue: 29(11), P. 2177 - 2189

Published: April 28, 2022

Language: Английский

Citations

58
DNA‐Damage‐Response‐Targeting Mitochondria‐Activated Multifunctional Prodrug Strategy for Self‐Defensive Tumor Therapy DOI
Paramesh Jangili, Na Kong, Ji Hyeon Kim

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(16)

Published: Feb. 8, 2022

We report a novel multifunctional construct, M1, designed explicitly to target the DNA damage response in cancer cells. M1 contains both floxuridine (FUDR) and protein phosphatase 2A (PP2A) inhibitor combined with GSH-sensitive linker. Further conjugation of triphenylphosphonium moiety allows undergo specific activation mitochondria, where mitochondria-mediated apoptosis is observed. Moreover, has enormous effects on genomic ascribed FUDR's primary function impeding DNA/RNA synthesis diminishing PP2A-activated repair pathways. Importantly, mechanistic studies highlight PP2A obtrusion FUDR/5-fluorouracil (5-FU) therapy underscore importance its inhibition harbor therapeutic potential. HCT116 cell xenograft-bearing mice that have low rate 5-FU show prominent effect emphasizing targeting strategies using tumor-specific microenvironment-activatable systems.

Language: Английский

Citations

47
Exploring the Use of Cold Atmospheric Plasma to Overcome Drug Resistance in Cancer DOI Creative Commons
Dzohara Murillo,

Carmen Huergo,

Borja Gallego

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(1), P. 208 - 208

Published: Jan. 14, 2023

Drug resistance is a major problem in cancer treatment, as it limits the effectiveness of pharmacological agents and can lead to disease progression. Cold atmospheric plasma (CAP) technology that uses ionized gas (plasma) generate reactive oxygen nitrogen species (RONS) kill cells. CAP novel approach for overcoming drug cancer. In recent years, there has been growing interest using enhance chemotherapy drugs. this review, we discuss mechanisms behind phenomenon explore its potential applications treatment. Going through existing literature on cancer, highlight challenges opportunities further research field. Our review suggests could be promising option warrants investigation.

Language: Английский

Citations

40