Immunomodulation of macrophages by methylglyoxal conjugated with chitosan nanoparticles against Sarcoma-180 tumor in mice

Chakrabarti, Adrita; Talukdar, Dipa; Pal, Aparajita; Ray, Manju

doi:10.1016/j.cellimm.2013.11.006

Cited by 41 publications

(28 citation statements)

References 41 publications

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“…[12][13][14] MG also inhibits tumor metastasis, enhances the immune response, and increases sensitivity to anti-tumor agents. [15][16][17][18] c-Myc is one of the most widely expressed human protooncogenes and is frequently overexpressed in colon cancer. 19 It has been shown to play an important role in the development and progression of this cancer.…”

Section: Introductionmentioning

confidence: 99%

Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression

Zhou

et al. 2016

Cancer Biology & Therapy

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Methylglyoxal (MG) is a highly reactive dicarbonyl compound exhibiting anti-tumor activity. The antitumor effects of MG have been demonstrated in some types of cancer, but its role in colon cancer and the mechanisms underlying this activity remain largely unknown. We investigated its role in human colon cancer and the underlying mechanism using human colon cancer cells and animal model. Viability, proliferation, and apoptosis were quantified in DLD-1 and SW480 colon cancer cells by using the Cell Counting Kit-8, plate colony formation assay, and flow cytometry, respectively. Cell migration and invasion were assessed by wound healing and transwell assays. Glucose consumption, lactate production, and intracellular ATP production also were assayed. The levels of c-Myc protein and mRNA were quantitated by western blot and qRT-PCR. The anti-tumor role of MG in vivo was investigated in a DLD-1 xenograft tumor model in nude mice. We demonstrated that MG inhibited viability, proliferation, migration, and invasion and induced apoptosis of DLD-1 and SW480 colon cancer cells. Treatment with MG reduced glucose consumption, lactate production, and ATP production and decreased c-Myc protein levels in these cells. Moreover, MG significantly suppressed tumor growth and c-Myc expression in vivo. Our findings suggest that MG plays an anti-tumor role in colon cancer. It inhibits cancer cell growth by altering the glycolytic pathway associated with downregulation of c-Myc protein. MG has therapeutic potential in colon cancer by interrupting cancer metabolism.

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Section: Introductionmentioning

confidence: 99%

Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression

Zhou

et al. 2016

Cancer Biology & Therapy

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“…Nano-MG were prepared by the method described previously, 21 with some modifications. In brief, initially a 100 mL solution of 0.3% low-molecular-weight chitosan (~40 kD) in dilute acetic acid (34.8 mM) was prepared by sonication for 45 minutes at 37°C.…”

Section: Synthesis Of Nanoparticlesmentioning

confidence: 99%

“…Mice treated with Nano-Chitosan (~15 mg/kg body weight/day) had neither any anticancer activity nor any toxic effect at this dose (results not presented), which is in accordance with our previous observation. 21 …”

Section: Animal Treatmentmentioning

confidence: 99%

“…18,19 It has also been reported that chitosan nanoparticles inhibit the proliferation of human gastric carcinoma cell line MGC-803. 20 Nanoparticles made of MG-loaded chitosan, prepared by Schiff's base conjugation between chitosan and MG designated as Nano-MG, 21 are expected to have sustained release of MG and hence improve its efficacy.…”

Section: Introductionmentioning

confidence: 99%

“…28 In the present study, we demonstrate the preparation of MG-loaded chitosan nanoparticles, their characterization, and their anticancer activity both in vitro and in vivo. These Nano-MG were more efficient and prepared in a more convenient way than our previously made Nano-MG. 21 This preparation also takes less time, thus making it more acceptable for production in pharmaceutical industries. The in vitro effect of Nano-MG was tested on HBL-100, A549, and Ehrlich ascites carcinoma (EAC) cell lines.…”

Section: Introductionmentioning

confidence: 99%

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Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect

Pal

Talukdar

Roy

et al. 2015

IJN

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Purpose The normal metabolite methylglyoxal (MG) specifically kills cancer cells by inhibiting glycolysis and mitochondrial respiration without much adverse effect upon normal cells. Though the anticancer property of MG is well documented, its gradual enzymatic degradation in vivo has prompted interest in developing a nanoparticulate drug delivery system to protect it and also to enhance its efficacy. Materials and methods MG-conjugated chitosan nanoparticles (Nano-MG) were prepared by conjugating the carbonyl group of MG with the amino group of chitosan polymer (Schiff’s base formation). Nano-MG were characterized in detail using the dynamic light scattering method, zeta potential measurement, Fourier transform infrared spectroscopy, and transmission electron microscopic analysis. Amount of MG anchored to Nano-MG, stability of Nano-MG, and in vitro release of MG from Nano-MG were estimated spectrophotometrically. Ehrlich ascites carcinoma (EAC) cells, human breast cancer cell line HBL-100, and lung epithelial adenocarcinoma cell line A549 were used as test systems to compare Nano-MG with bare MG in vitro. Cytotoxicity to EAC cells was evaluated by the trypan blue dye exclusion test, and cell viability of HBL-100 and A549 cells were studied using 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis of HBL-100 cells was assessed by flow cytometry and confocal microscopy. In vivo studies were performed on both EAC cells inoculated and also in sarcoma-180-induced solid tumor-bearing Swiss albino mice to assess the anticancer activity of Nano-MG in comparison to bare MG with varying doses, times, and administrative routes. Results Fourier transform infrared spectroscopy revealed the presence of imine groups in Nano-MG due to conjugation of the amino group of chitosan and carbonyl group of MG with diameters of nanoparticles ranging from 50–100 nm. The zeta potential of Nano-MG was +21 mV and they contained approximately 100 μg of MG in 1 mL of solution. In vitro studies with Nano-MG showed higher cytotoxicity and enhanced rate of apoptosis in the HBL-100 cell line in comparison with bare MG, but no detrimental effect on normal mouse myoblast cell line C2C12 at the concerned doses. Studies with EAC cells also showed increased cell death of nearly 1.5 times. Nano-MG had similar cytotoxic effects on A549 cells. In vivo studies further demonstrated the efficacy of Nano-MG over bare MG and found them to be about 400 times more potent in EAC-bearing mice and nearly 80 times more effective in sarcoma-180-bearing mice. Administration of ascorbic acid and creatine during in vivo treatments augmented the anticancer effect of Nano-MG. Conclusion The results clearly indicate that Nano-MG may constitute a promising tool in anticancer therapeutics in the near future.

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Methods for Implant Acceptance and Wound Healing: Material Selection and Implant Location Modulate Macrophage and Fibroblast Phenotypes

Boddupalli

Zhu

Bratlie

2016

Adv Healthcare Materials

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This review focuses on materials and methods used to induce phenotypic changes in macrophages and fibroblasts. Herein, we give a brief overview on how changes in macrophages and fibroblasts phenotypes are critical biomarkers for identification of implant acceptance, wound healing effectiveness, and are also essential for evaluating the regenerative capabilities of some hybrid strategies that involve the combination of natural and synthetic materials. The different types of cells present during the host response have been extensively studied for evaluating the reaction to different materials and there are varied material approaches towards fabrication of biocompatible substrates. We discuss how natural and synthetic materials have been used to engineer desirable outcomes in lung, heart, liver, skin, and musculoskeletal implants, and how certain properties such as rigidity, surface shape, and porosity play key roles in the progression of the host response. Several fabrication strategies are discussed to control the phenotype of infiltrating macrophages and fibroblasts: decellularization of scaffolds, surface coatings, implant shape, and pore size apart from biochemical signaling pathways that can inhibit or accelerate unfavorable host responses. It is essential to factor all the different design principles and material fabrication criteria for evaluating the choice of implant materials or regenerative therapeutic strategies.

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Immunomodulation of macrophages by methylglyoxal conjugated with chitosan nanoparticles against Sarcoma-180 tumor in mice

Cited by 41 publications

References 41 publications

Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression

Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression

Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect

Methods for Implant Acceptance and Wound Healing: Material Selection and Implant Location Modulate Macrophage and Fibroblast Phenotypes

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Immunomodulation of macrophages by methylglyoxal conjugated with chitosan nanoparticles against Sarcoma-180 tumor in mice

Cited by 41 publications

References 41 publications

Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression

Methylglyoxal suppresses human colon cancer cell lines and tumor growth in a mouse model by impairing glycolytic metabolism of cancer cells associated with down-regulation of c-Myc expression

Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of&nbsp;its anticancer effect

Methods for Implant Acceptance and Wound Healing: Material Selection and Implant Location Modulate Macrophage and Fibroblast Phenotypes

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Nanofabrication of methylglyoxal with chitosan biopolymer: a potential tool for enhancement of its anticancer effect