Antineoplastic properties of zafirlukast against hepatocellular carcinoma via activation of mitochondrial mediated apoptosis

Kumar, Pranesh; Agarwal, Aakriti; Singh, Ashok Kumar; Gautam, Anurag; Chakraborti, Sreemoyee; Kumar, Umesh; Kumar, Dinesh; Bhattacharya, Bolay; Panda, Parthasarathi; Saha, Banani; Qidwai, Tabish; Maity, Biswanath; Saha, Sudipta

doi:10.1016/j.yrtph.2019.104489

Cited by 13 publications

(13 citation statements)

References 39 publications

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“…The elevation of these pigments and normalized after oral treatment also specify the antineoplastic property of DI against HCC. CC rats also had vacuole development and abnormally shaped nuclei and cytoplasm, according to histological examinations (Kumar et al, 2019;Maurya et al, 2019). This vacuole formation was decreased after DI and 5-FU treatments, and HCC condition was improved and clearly observed through histopathology.…”

Section: Discussionmentioning

confidence: 90%

“…The groups of animals were distributed into five categories: Group 1 (Normal Control, NC) received 0.25% CMC (2 ml/kg), Group 2 (Carcinogen Control, CC) received N-nitrosodiethylamine (DEN, 100 mg/kg, i.p. once a week for total 6 weeks) (Kumar et al, 2019), Group 3 (Positive Control, PC) received DEN + 5flurouracil (5-FU, 10 mg/kg, i.p. for total 15 days after HCC induction), Group 4 (Treatment 1) received DEN + DI (T1, 100 mg/kg, orally for total 15 days after HCC induction), and Group 5 (Treatment 2) received DEN + DI (T2, 200 mg/kg, orally for 15 days after HCC induction) (Singh et al, 2018).…”

Section: Design Of Experimentsmentioning

confidence: 99%

“…Caspase-3 and caspase-9 were supplied by Geno Technology Inc., Noida, India. ELISA was used to assess hepatic tissues in accordance with the manufacturer's instructions (available online) (Kumar et al, 2019;Maurya et al, 2019).…”

Section: Estimation Of Cytokines By Elisamentioning

confidence: 99%

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Preclinical Evaluation of Dimethyl Itaconate Against Hepatocellular Carcinoma via Activation of the e/iNOS-Mediated NF-κB–Dependent Apoptotic Pathway

et al. 2022

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Hepatocellular carcinoma (HCC) is one of the most common tumors affecting a large population worldwide, with the fifth and seventh greatest mortality rates among men and women, respectively, and the third prime cause of mortality among cancer victims. Dimethyl itaconate (DI) has been reported to be efficacious in colorectal cancer by decreasing IL-1β release from intestinal epithelial cells. In this study, diethylnitrosamine (DEN)-induced HCC in male albino Wistar rats was treated with DI as an anticancer drug. The function and molecular mechanism of DI against HCC in vivo were assessed using histopathology, enzyme-linked immunosorbent assay (ELISA), and Western blot studies. Metabolomics using 1H-NMR was used to investigate metabolic profiles. As per molecular insights, DI has the ability to trigger mitochondrial apoptosis through iNOS- and eNOS-induced activation of the NF-κB/Bcl-2 family of proteins, CytC, caspase-3, and caspase-9 signaling cascade. Serum metabolomics investigations using 1H-NMR revealed that aberrant metabolites in DEN-induced HCC rats were restored to normal following DI therapy. Furthermore, our data revealed that the DI worked as an anti-HCC agent. The anticancer activity of DI was shown to be equivalent to that of the commercial chemotherapeutic drug 5-fluorouracil.

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Section: Discussionmentioning

confidence: 90%

Section: Design Of Experimentsmentioning

confidence: 99%

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Preclinical Evaluation of Dimethyl Itaconate Against Hepatocellular Carcinoma via Activation of the e/iNOS-Mediated NF-κB–Dependent Apoptotic Pathway

et al. 2022

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“…However, According to the reported literature [22][23][24], rats also have significant oxidative stress, even apoptosis and liver damage response at high doses (>1 g/kg) of APAP even under resistant state. Additionally, the use of rats for metabolomics and organ damage studies exhibit obvious advantages over mice [25,26]. Thus, forty male Sprague-Dawley rats (180 ± 20 g) at age of six weeks old were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd (SCXK 2016-0011).…”

Section: Animalsmentioning

confidence: 99%

Hepatoprotective Effect of Citrus aurantium L. Against APAP-induced Liver Injury by Regulating Liver Lipid Metabolism and Apoptosis

Shu

et al. 2020

Int. J. Biol. Sci.

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Acetaminophen (APAP) refers to a medication used to manage pain and fever symptoms, but it always causes liver injury when overdosed. Zhishi, dried young fruit of Citrus aurantium L., is a famous Citrus herbal medicine in Asian countries which is rich in dietary phenolic substances. In this study, the mechanism of Zhishi protected against APAP-induced liver injury was studied more deeply by metabolomic strategy and pharmacological study. The metabolomics results demonstrated that Zhishi can prevent the APAP-induced liver injury model by regulating liver metabolic disorders in glycerophospholipid metabolism, fatty acid biosynthesis and glycerolipid metabolism. Moreover, it is confirmed that Zhishi blocked apoptosis of APAP-induced BRL-3A cell by simultaneously regulating p53 up-regulated apoptosis regulator (PUMA), AMPK-SIRT1 and JNK1 signaling pathways. Our findings indicated that Zhishi exhibited a hepaprotective effect against APAP-induced liver necrosis by inhibiting the PUMA and reversing disorder of liver lipid metabolism which could assist in improving the clinical outcomes of chemical-induced liver injury.

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“…The groups classified as the normal control (NC); Group I administered orally with carboxymethyl cellulose (0.25%, 2 mL/kg body weight); carcinogen control (CC); Group II, i.p. administered with (100 mg/kg body weight) N-nitrosodiethylamine (NDEA), for 6 weeks (one time in a week); 38 Group III (IMS), NDEA+IMS (10 mg/kg body weight, given after HCC induction for 21 days); 13 Group IV (IMS-LCNPs), NDEA +IMS-LCNPs (10 mg/kg, administered orally, after HCC induction for 21 days); and Group V (IMS-LF-LCNPs), NDEA+IMS-LF-LCNPs (10 mg/kg, orally, given after HCC induction for 21 days). After 21 days of treatment, all surviving rats were sacrificed.…”

Section: Introductionmentioning

confidence: 99%

Fabrication of Imatinib Mesylate-Loaded Lactoferrin-Modified PEGylated Liquid Crystalline Nanoparticles for Mitochondrial-Dependent Apoptosis in Hepatocellular Carcinoma

Nisha

Kumar

et al. 2020

Mol. Pharmaceutics

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Hepatocellular carcinoma (HCC) is a major cause of concern as it has substantial morbidity associated with it. Previous reports have ascertained the antiproliferative activity of imatinib mesylate (IMS) against diverse types of carcinomas, but limited bioavailability has also been reported. The present study envisaged optimized IMS-loaded lactoferrin (LF)-modified PEGylated liquid crystalline nanoparticles (IMS-LF-LCNPs) for effective therapy of IMS to HCC via asialoglycoprotein receptor (ASGPR) targeting. Results displayed that IMS-LF-LCNPs presented an optimum particle size of 120.40 ± 2.75 nm, a zeta potential of +12.5 ± 0.23 mV, and 73.94 ± 2.69% release. High-resolution transmission electron microscopy and atomic force microscopy were used to confirm the surface architecture of IMS-LF-LCNPs. The results of cytotoxicity and 4,6-diamidino-2-phenylindole revealed that IMS-LF-LCNPs had the highest growth inhibition and significant apoptotic effects. Pharmacokinetics and biodistribution studies showed that IMS-LF-LCNPs have superior pharmacokinetic performance and targeted delivery compared to IMS-LCNPs and plain IMS, which was attributed to the targeting action of LF that targets the ASGPR in hepatic cells. Next, our in vivo experiment established that the HCC environment existed due to suppression of BAX, cyt c, BAD, e-NOS, and caspase (3 and 9) genes, which thus owed upstream expression of Bcl-xl, iNOS, and Bcl-2 genes. The excellent therapeutic potential of IMS-LF-LCNPs began the significant stimulation of caspase-mediated apoptotic signals accountable for its anti-HCC prospect. 1 H nuclear magnetic resonance (serum) metabolomics revealed that IMS-LF-LCNPs are capable of regulating the disturbed levels of metabolites linked to HCC triggered through N-nitrosodiethylamine. Therefore, IMS-LF-LCNPs are a potentially effective formulation against HCC.

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Antineoplastic properties of zafirlukast against hepatocellular carcinoma via activation of mitochondrial mediated apoptosis

Cited by 13 publications

References 39 publications

Preclinical Evaluation of Dimethyl Itaconate Against Hepatocellular Carcinoma via Activation of the e/iNOS-Mediated NF-κB–Dependent Apoptotic Pathway

Preclinical Evaluation of Dimethyl Itaconate Against Hepatocellular Carcinoma via Activation of the e/iNOS-Mediated NF-κB–Dependent Apoptotic Pathway

Hepatoprotective Effect of Citrus aurantium L. Against APAP-induced Liver Injury by Regulating Liver Lipid Metabolism and Apoptosis

Fabrication of Imatinib Mesylate-Loaded Lactoferrin-Modified PEGylated Liquid Crystalline Nanoparticles for Mitochondrial-Dependent Apoptosis in Hepatocellular Carcinoma

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