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Immunohistochemical staining of tumor section for apoptosis marker. A control group, B MEF group, C IR group, D IR + MEF group. IR increased immunoreactivity of caspase-3. MEF with IR was more effective. Magnification: × 40, Scale bar: 100 μm. MEF mefenamic acid, IR irradiation
Source publication
Although radiotherapy is an effective strategy for cancer treatment, tumor resistance to ionizing radiation (IR) and its toxic effects on normal tissues are limiting its use. The aim of this study is to evaluate the anti-cancer effects of mefenamic acid (MEF), as an approved medicine, and its combination with IR against colon tumor cells in mice. T...
Citations
... Colon cancer, liver cancer, cervical cancer. Study: [127][128][129][130] , including indomethacin and diclofenac, as well as Celecoxib can directly inhibit COX2. Specific iNOS inhibitors, such as acetamidine compounds like 1400 W, demonstrate highly efficient and targeted effects. ...
Nitric oxide (NO) and reactive nitrogen species (RNS) exert profound biological impacts dictated by their chemistry. Understanding their spatial distribution is essential for deciphering their roles in diverse biological processes. This review establishes a framework for the chemical biology of NO and RNS, exploring their dynamic reactions within the context of cancer. Concentration-dependent signaling reveals distinctive processes in cancer, with three levels of NO influencing oncogenic properties. In this context, NO plays a crucial role in cancer cell proliferation, metastasis, chemotherapy resistance, and immune suppression. Increased NOS2 expression correlates with poor survival across different tumors, including breast cancer. Additionally, NOS2 can crosstalk with the proinflammatory enzyme cyclooxygenase-2 (COX-2) to promote cancer progression. NOS2 and COX-2 co-expression establishes a positive feed-forward loop, driving immunosuppression and metastasis in estrogen receptor-negative (ER-) breast cancer. Spatial evaluation of NOS2 and COX-2 reveals orthogonal expression, suggesting the unique roles of these niches in the tumor microenvironment (TME). NOS2 and COX2 niche formation requires IFN-γ and cytokine-releasing cells. These niches contribute to poor clinical outcomes, emphasizing their role in cancer progression. Strategies to target these markers include direct inhibition, involving pan-inhibitors and selective inhibitors, as well as indirect approaches targeting their induction or downstream effectors. Compounds from cruciferous vegetables are potential candidates for NOS2 and COX-2 inhibition offering therapeutic applications. Thus, understanding the chemical biology of NO and RNS, their spatial distribution, and their implications in cancer progression provides valuable insights for developing targeted therapies and preventive strategies.
... MEF, along with other fenamates, has demonstrated an anticancer effect also in cervical-uterine (Soriano-Hernandez et al. 2015) and prostate cancer cells (Soriano-Hernández et al. 2012). But it has also been demonstrated in tumors from animal models of colon cancer (Seyyedi et al. 2022), and its anti-cancer effect has even been tested in human clinical trials in prostate cancer (Guzman-Esquivel et al. 2020). ...
Background
This work aimed to prepare niosomal formulations of an anticancer agent [mefenamic acid (MEF)] to enhance its cancer targeting. ¹³¹I was utilized as a radiolabeling isotope to study the radio-kinetics of MEF niosomes.
Methods
niosomal formulations were prepared by the ether injection method and assessed for entrapment efficiency (EE%), zeta potential (ZP), polydispersity index (PDI) and particle size (PS). MEF was labeled with ¹³¹I by direct electrophilic substitution reaction through optimization of radiolabeling-related parameters. In the radio-kinetic study, the optimal ¹³¹I-MEF niosomal formula was administered intravenously (I.V.) to solid tumor-bearing mice and compared to I.V. ¹³¹I-MEF solution as a control.
Results
the average PS and ZP values of the optimal formulation were 247.23 ± 2.32 nm and − 28.3 ± 1.21, respectively. The highest ¹³¹I-MEF labeling yield was 98.7 ± 0.8%. The biodistribution study revealed that the highest tumor uptake of ¹³¹I-MEF niosomal formula and ¹³¹I-MEF solution at 60 min post-injection were 2.73 and 1.94% ID/g, respectively.
Conclusion
MEF-loaded niosomes could be a hopeful candidate in cancer treatment due to their potent tumor uptake. Such high targeting was attributed to passive targeting of the nanosized niosomes and confirmed by radiokinetic evaluation.
... In addition, it can reduce cancer cell proliferation, progression, angiogenesis, and invasion [89]. It has also been shown that MFA in combination with ionizing radiation increases apoptosis in tumor tissues and protects against DNA damage caused by ionizing radiation [90,91]. MFA is a class of NSAIDs that has high antiproliferative activity, whereas salicylates, the most common drugs used in clinical studies, show a relatively weak antiproliferative effect [92]. ...
Simple Summary
Prostate cancer is a serious health problem for men around the world, and it is often caused by inflammation in the prostate gland. The authors of this article explore how a group of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs) can help prevent and treat this disease by reducing inflammation and interfering with the growth and survival of cancer cells. We describe the various mechanisms by which NSAIDs can affect prostate cancer, such as triggering cell death, halting cell division, and cutting off blood supply. We also discuss the evidence from previous studies that support the use of NSAIDs as anti-cancer agents, either alone or in combination with other treatments. NSAIDs have a lot of promise as potential drugs for prostate cancer, but more research to understand their optimal dosage, timing, and safety is needed.
Abstract
Prostate cancer (PC) is the second most common type of cancer and the leading cause of death among men worldwide. Preventing the progression of cancer after treatments such as radical prostatectomy, radiation therapy, and hormone therapy is a major concern faced by prostate cancer patients. Inflammation, which can be caused by various factors such as infections, the microbiome, obesity and a high-fat diet, is considered to be the main cause of PC. Inflammatory cells are believed to play a crucial role in tumor progression. Therefore, nonsteroidal anti-inflammatory drugs along with their effects on the treatment of inflammation-related diseases, can prevent cancer and its progression by suppressing various inflammatory pathways. Recent evidence shows that nonsteroidal anti-inflammatory drugs are effective in the prevention and treatment of prostate cancer. In this review, we discuss the different pathways through which these drugs exert their potential preventive and therapeutic effects on prostate cancer.
... The top candidates for colon cancer generated using the proteomic signature pipeline (left, red text) included alpremilast and mebendazole (Nygren et al., 2013;Nygren and Larsson, 2014;Williamson et al., 2016;Nishi et al., 2017;Petersen and Baird, 2021), however mechanistic understanding using the whole signature is lacking. Conversely, the candidates generated via the interactomic signature pipeline (left, blue text) included telmisartan, nabumetone, fenofibrate, and mefenamic acid (Ozeki et al., 2013;Mielczarek-Puta et al., 2020;Lee et al., 2014;Roy et al., 2001b;Kong et al., 2021;Seyyedi et al., 2022;Hosseinimehr et al., 2019), which may be exerting their therapeutic effects via impacting multiple pathways implicated in colon cancer simultaneously (Myung and Kim, 2008;Bahrami et al., 2018;Luo et al., 2019;Ungaro et al., 2020). Similarly, the top candidates for migraine disorders generated by the proteomic signature pipeline (right, red text) included methylergometrine and betaxolol (Tfelt-Hansen et al., 1987;Koehler and Tfelt-Hansen, 2008), both of which can be seen as trivial due to other members of their respective drug classes already being commonly used treatments for migraines. ...
The two most common reasons for attrition in therapeutic clinical trials are efficacy and safety. We integrated heterogeneous data to create a human interactome network to comprehensively describe drug behavior in biological systems, with the goal of accurate therapeutic candidate generation. The Computational Analysis of Novel Drug Opportunities (CANDO) platform for shotgun multiscale therapeutic discovery, repurposing, and design was enhanced by integrating drug side effects, protein pathways, protein-protein interactions, protein-disease associations, and the Gene Ontology, and complemented with its existing drug/compound, protein, and indication libraries. These integrated networks were reduced to a "multiscale interactomic signature" for each compound that describe its functional behavior as vectors of real values. These signatures are then used for relating compounds to each other with the hypothesis that similar signatures yield similar behavior. Our results indicated that there is significant biological information captured within our networks (particularly via side effects) which enhance the performance of our platform, as evaluated by performing all-against-all leave-one-out drug-indication association benchmarking as well as generating novel drug candidates for colon cancer and migraine disorders corroborated via literature search. Further, drug impacts on pathways derived from computed compound-protein interaction scores served as the features for a random forest machine learning model trained to predict drug-indication associations, with applications to mental disorders and cancer metastasis highlighted. This interactomic pipeline highlights the ability of Computational Analysis of Novel Drug Opportunities to accurately relate drugs in a multitarget and multiscale context, particularly for generating putative drug candidates using the information gleaned from indirect data such as side effect profiles and protein pathway information.
... The reversible m 6 A mark that contributes to several cancer hallmarks may offer new therapeutic opportunities, and rapid advancements are being made in this direction. In 2014, meclofenamic acid (MA) was identified as FTO inhibitor,132 and the anticancer activity of MA and its derivative133,134 was successfully tested in preclinical studies.[133][134][135][136][137] Since MA is already used in the clinic, a drug repurposing approach may represent a promising strategy in cancer.Several molecules targeting m 6 A effectors, mainly writers and erasers, have been developed133,[138][139][140][141][142][143][144][145][146][147][148][149][150][151] (Table 1). ...
Chromatin has an extremely flexible structure that allows the fine regulation of gene expression. To orchestrate this process, small chemical modifications are dynamically added or removed on DNA, RNA and histone substrates. Epigenetic modifications govern a plethora of key cellular functions, whose dysregulation contributes to oncogenesis. The interrelationship between (irreversible) genetic mutations and (reversible) epigenetic alterations and how this crosstalk regulates gene expression has long been a major area of interest. Marks modulating the RNA code (epitranscriptome), such as the well‐studied N⁶‐methyladenosine (m⁶A), are known to influence stability, metabolism and life cycle of many mRNAs, including cancer‐associated transcripts. Together, epigenetic and epitranscriptomic pathways therefore control the entire cellular expression profile and, eventually, cell fate. Recently, previously undescribed crosstalk between these two pathways has started to be unrevealed. For example, m⁶A and its effectors cooperate with histone modifications to localize chromatin‐modifying complexes to their target regions. Epigenetic marks governing the expression of m⁶A factors can also be found at specific genetic loci. m⁶A itself can mark noncoding RNAs (including lncRNAs, circRNAs and miRNAs), influencing their structure, maturation and function. These interactions affect both cell physiology and pathology. Clear evidence that dysregulation of this network plays a role in cancer has emerged, suggesting a new layer of complexity in the landscape of gene expression. Here, we summarize current knowledge on the interplay between m⁶A epitranscriptome and epigenome, focusing on cancer processes. We also discuss strategies to target m⁶A machinery for future therapeutic intervention.
Cancer is one of the most difficult diseases to treat in modern medicine. Annually, many articles are published that propose various ways for preventing carcinogenesis. Furthermore, research into cancer treatments is carried out with minimal side effects. The most common non-invasive cancer treatments include chemotherapy, targeted therapy, radiotherapy, and immunotherapy. Low effectiveness of chemo-radiation therapy and normal tissue toxicity caused by these treatments are two of the most difficult challenges. Some medicines have been recommended as adjuvants to increase tumor responses while also reducing normal tissue damage. Cerium oxide as a nanoparticle (nanoceria, CNPs) has recieved a lot of interest as a way to control tumor and normal tissue responses to various cancer treatment regimens. In vitro and in vivo studies demonstrate that it can reduce chemo-radiation toxicity in normal tissues as an antioxidant and anti-inflammatory agent. Furthermore, it has the ability to make cancer cells more sensitive to both chemotherapy and radiotherapy. In this paper, we reviewed the potential role of nanoceria for preserving normal tissues and sensitization of cancer cells in combination with different cancer treatment modalities. © 2022, Mazandaran University of Medical Sciences. All rights reserved.
