A comprehensive review on methotrexate containing nanoparticles; an appropriate tool for cancer treatment

Shariatifar, Hanifeh; Ranjbarian, Fateme; Hajiahmadi, Fahimeh; Farasat, Alireza

doi:10.1007/s11033-022-07782-7

Cited by 9 publications

(5 citation statements)

References 71 publications

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“…MTX is an old drug that has been used worldwide for the treatment of various diseases such as autoimmune disease, rheumatoid arthritis, and cancer. [26,27] However, little is known about its efficacy in liver cancer. In this study, we established the preclinical therapeutic efficacy of MTX against mouse liver cancer, which mimicked a subtype of human HCC with concurrent CTNNB1- activated mutation and HBV infection.…”

Section: Discussionmentioning

confidence: 99%

Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis

Liu,

Wu,

Zhang

et al. 2023

Chinese Medical Journal

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Background: Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 (CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Methods: Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 (β-cateninΔ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus (HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. Results: MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. Conclusion: MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

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Section: Discussionmentioning

confidence: 99%

Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis

Liu,

Wu,

Zhang

et al. 2023

Chinese Medical Journal

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“…Methotrexate (MTX) is a well-known chemotherapy drug, and its anti-tumor mechanism is through inhibiting purine synthesis, inhibiting the S-phase of the cell cycle, and ultimately triggering cell apoptosis [ 116 ]. Although MTX has significant effects in the treatment of leukemia, breast cancer, head and neck cancer and other cancer types, it has a wide range of side effects, including bone marrow suppression, immunosuppression, mucositis, hepatotoxicity, alopecia, nausea and vomiting [ 117 ]. The combination of 6-shogaol and MTX not only enhances its therapeutic effect but also reduces its adverse reactions during the anti leukaemia process.…”

Section: Synergiesmentioning

confidence: 99%

Anticancer perspective of 6-shogaol: anticancer properties, mechanism of action, synergism and delivery system

Jia,

Li,

Meng

et al. 2023

Chin Med

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Cancer is a malignant disease that has plagued human beings all the time, but the treatment effect of commonly used anticancer drugs in clinical practice is not ideal by reason of their drug tolerance and Strong adverse reactions to patients. Therefore, it is imperative to find effective and low-toxic anticancer drugs. Many research works have shown that natural products in Chinese herbal medicine have great anticancer potential, such as 6-shogaol, a monomer composition obtained from Chinese herbal ginger, which has been confirmed by numerous in vitro or vivo studies to be an excellent anti-cancer active substance. In addition, most notably, 6-shogaol has different selectivity for normal and cancer cells during treatment, which makes it valuable for further research and clinical development. Therefore, this review focus on the anti-cancer attributes, the mechanism and the regulation of related signaling pathways of 6-shogaol. In addition, its synergy with commonly used anticancer drugs, potential drug delivery systems and prospects for future research are discussed. This is the first review to comprehensively summarize the anti-cancer mechanism of 6-shogaol, hoping to provide a theoretical basis and guiding significance for future anti-cancer research and clinical development of 6-shogaol. Graphical Abstract

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“…Methotrexate (MTX) has been extensively used in the clinical treatment of leukaemia and a variety of other tumours 1 . MTX is an inhibitor of dihydrofolate reductase 2 .…”

Section: Introductionmentioning

confidence: 99%

Aucubin alleviates methotrexate‐induced enteritis in rats by inducing autophagy

Yang

Lang

Zhao

et al. 2023

Clin Exp Pharma Physio

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One of the toxic side effects of methotrexate (MTX) is enteritis. Aucubin, an iridoid glycoside derived from traditional medicinal herbs, has been proven to have anti‐inflammation, anti‐apoptosis and anti‐oxidation properties. This work explored the effect and mechanism of aucubin in treating MTX‐induced enteritis in a rat model. Two doses of aucubin (5 and 10 mg/kg) were adopted for the assessment of its pharmacological activity. We observed that in rats with MTX‐induced enteritis, the body weight and small intestinal weight decreased. The intestine barrier was injured, as reflected by pathological examinations and an increase in D‐lactate and diamine oxidase concentration in serum. Intestinal inflammation was shown by the observation of macrophages in the intestine and the concentrations of inflammatory cytokines tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) in serum. The NLR family pyrin domain containing 3 (NLRP3) inflammasome was shown to be activated by the enhancement of NLRP3, cleaved‐caspase 1, IL‐18 and IL‐1β. Moreover, autophagy was reflected by transmission electron microscopy as slightly induced, along with changes in autophagy‐related markers microtubule‐associated protein 1 light chain 3 (LC3) and Beclin1. Remarkably, aucubin treatment attenuated the MTX‐induced disease activity index increase, intestinal damage, inflammatory response and NLRP3 inflammasome activation, but provoked autophagy. Rapamycin, an autophagy activator, showed similar therapeutic effects to aucubin on MTX‐induced enteritis. However, 3‐methyladenine, an autophagy inhibitor, reversed the protective effects of aucubin. These findings prompted the hypothesis that aucubin alleviates MTX‐induced enteritis by aggravating autophagy. This study might provide evidence for further investigation on the therapeutic role of aucubin in MTX‐resulted enteritis.

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A comprehensive review on methotrexate containing nanoparticles; an appropriate tool for cancer treatment

Cited by 9 publications

References 71 publications

Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis

Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis

Anticancer perspective of 6-shogaol: anticancer properties, mechanism of action, synergism and delivery system

Aucubin alleviates methotrexate‐induced enteritis in rats by inducing autophagy

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