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Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro.

Bisphosphonates (BPs) are an emerging class of drugs mostly used in the palliative care of cancer patients. We investigated the in vitro activity of the most potent antiresorptive BP, zoledronic acid (ZOL), on the growth and survival of three human pancreatic cancer (PC) cell lines (BxPC-3, CFPAC-1 and PANC-1). Pancreatic cancer frequently has a dysregulated p21(ras) pathway and therefore appears to be a suitable target for BPs that interfere with the prenylation of small GTP-binding proteins such as p21(ras). We found that ZOL induces growth inhibition (IC(50):10-50 micro M) and apoptotic dea

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… After final washes, coverslips were mounted on the dishes using a 50% solution of glycerol in PBS. The cells were examined under a LEICA TCS SP2 confocal microscope. Statistical analysis Results are expressed as mean ±s.e. …

Role of Protein Kinase CK2 in Aberrant Lipid Metabolism in Cancer.

Uncontrolled proliferation is a feature defining cancer and it is linked to the ability of cancer cells to effectively adapt their metabolic needs in response to a harsh tumor environment. Metabolic reprogramming is considered a hallmark of cancer and includes increased glucose uptake and processing, and increased glutamine utilization, but also the deregulation of lipid and cholesterol-associated signal transduction, as highlighted in recent years. In the first part of the review, we will i) provide an overview of the major types of lipids found in eukaryotic cells and their importance as med

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… The storage form of fatty acids is represented by triacylglycerols (TAGs) where all three hydroxyl groups on glycerol are esterified with a fatty acid. Most fatty acids are provided through the diet; however, complex biochemical reactions ensure their de novo synthesis from small molecules [ 2 ]. … Phospholipids are polar lipids composed of glycerol, two fatty acids, a phosphate group and a polar group such as choline, serine or ethanolamine. Phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine are major components of all cellular membranes and can form bilayers. …

Advances in Understanding Mitochondrial MicroRNAs (mitomiRs) on the Pathogenesis of Triple-Negative Breast Cancer (TNBC).

Triple-negative breast cancer (TNBC) is characterized by poor outcome and the most challenging breast cancer type to treat worldwide. TNBC manifests distinct profile of mitochondrial functions, which dictates reprogrammed metabolism, fosters tumor progression, and notably serves as therapeutic targets. Mitochondrial microRNAs (mitomiRs) are a group of microRNAs that critically modulate mitochondrial homeostasis. By a pathway-centric manner, mitomiRs tightly orchestrate metabolic reprogramming, redox status, cell apoptosis, mitochondrial dynamics, mitophagy, mitochondrial DNA (mtDNA) maintenanc

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… Zhang et al. demonstrated that overexpression of miR-1 exerts a tumor-suppressive effect by simultaneously targeting mitophagy-associated genes including MINOS1 (mitochondrial inner membrane organizing system 1), GPD2 (glycerol-3-phosphate dehydrogenase 2), and LRPPRC (leucine-rich pentatricopeptide-repeat …

The paracrine effects of tumor-resident mesenchymal stem/stromal cells in the microenvironment of brain metastases.

BACKGROUND: Tumor-resident mesenchymal stem/stromal cells (MSCs) were identified in several cancers, and were implicated in regulating multiple aspects of tumor progression. However, the role of tumor-resident MSCs in the pathophysiology of brain metastases (BrMs) -the most prevalent type of malignant brain tumor- is currently unknown, and was investigated in this study. METHODS: Tumor-resident MSCs were isolated from fresh human lung-BrM tissues (n=3) and were phenotypically assessed in FFPE lung-BrM tissues (n=11). The paracrine effects of BrM-MSCs on neutrophil granulocytes and endothelial

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… The cells were removed by centrifugation, and the resulting supernatants were subsequently mixed with zymogram sample buffer at a final concentration of 80 mM Tris pH 6.8, 1% SDS, 4% glycerol and 0.006% bromophenol blue. …

IL-20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer.

Bone is a common site of metastasis in lung cancer, but the regulatory mechanism remains incompletely understood. Osteoclasts are known to play crucial roles in osteolytic bone metastasis by digesting bone matrix and indirectly enhancing tumor colonization. In this study, we found that IL receptor 20 subunit β (IL-20RB) mediated a direct tumoral response to osteoclasts. Tumoral expression of IL-20RB was associated with bone metastasis of lung cancer, and functionally, IL-20RB promoted metastatic growth of lung cancer cells in bone. Mechanistically, tumor cells induced osteoclasts to secrete th

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… Forty-eight hours later, the medium was discarded and cells were lysed with 60 μL luciferase lysis buffer (2 mM EDTA, 20 mM DTT, 10% glycerol, 1% Triton X-100 and 25 mM Tris-base, pH 7.8) for 1 hour at room temperature; 10 μL lysate was added with 30 μL firefly luciferase assay buffer (25 mM glycylglycine …

Aplidin (plitidepsin) is a novel anti-myeloma agent with potent anti-resorptive activity mediated by direct effects on osteoclasts.

Despite recent progress in its treatment, Multiple Myeloma (MM) remains incurable and its associated bone disease persists even after complete remission. Thus, identification of new therapeutic agents that simultaneously suppress MM growth and protect bone is an unmet need. Herein, we examined the effects of Aplidin, a novel anti-cancer marine-derived compound, on MM and bone cells. In vitro, Aplidin potently inhibited MM cell growth and induced apoptosis, effects that were enhanced by dexamethasone (Dex) and bortezomib (Btz). Aplidin modestly reduced osteocyte/osteoblast viability and decreas

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… Cell lysates (25 μg) were boiled in the presence of sodium dodecyl sulfate (SDS) sample buffer (0.5 M Tris–HCl, pH 6.8, 10% wt/vol SDS, 10% glycerol, 0.05% wt/vol bromophenol blue) for 5 minutes and subjected to electrophoresis on 4% to 20% SDS -PAGE (Bio-Rad Laboratories, Hercules, CA, USA). …

Liposomes for the Treatment of Brain Cancer-A Review.

Due to their biocompatibility, non-toxicity, and surface-conjugation capabilities, liposomes are effective nanocarriers that can encapsulate chemotherapeutic drugs and facilitate targeted delivery across the blood-brain barrier (BBB). Additionally, strategies have been explored to synthesize liposomes that respond to internal and/or external stimuli to release their payload controllably. Although research into liposomes for brain cancer treatment is still in its infancy, these systems have great potential to fundamentally change the drug delivery landscape. This review paper attempts to consol

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… Glycerophospholipids have a hydrophilic glycerol head group that is esterified to hydrophobic alkyl side chains [ 86 ]. … Additionally, the type of bonding (ether or ester) between glycerol and the aliphatic chains results in distinct glycerophospholipids [ 87 ]. These bilayers of phospholipids are composed of hydrophilic heads and hydrophobic tails. …

An expanding horizon of complex injectable products: development and regulatory considerations.

There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is either market-driven or technology-driven to improve the overall therapeutic efficacy and patients' quality of life. The pharmaceutical industry has experienced rapid growth in the area of complex injectable products because of their effectiveness in the unmet market. These novel parenteral products, viz, the nanoparticles, liposomes, microspheres, suspensions, and emulsions, have proven their worth as "Safe and Effective" produ

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… . | Diprivan ® | Propofol | Small molecule | Emulsion | 10 mg/mL | Soybean oil, glycerol, egg lecithin, disodium edetate anhydrous | Inducing general anesthesia | I.V. … Additionally, certain amphiphilic polymers like cetyldimethicone coplyol (Abil EM 90), polysiloxane, and poly-glycerol-poly-ricinolate are employed as stabilizers for various emulsion, double emulsions, and suspensions. …

Biosynthesis of anticancer phytochemical compounds and their chemistry.

Cancer is a severe health issue, and cancer cases are rising yearly. New anticancer drugs have been developed as our understanding of the molecular mechanisms behind diverse solid tumors, and metastatic malignancies have increased. Plant-derived phytochemical compounds target different oncogenes, tumor suppressor genes, protein channels, immune cells, protein channels, and pumps, which have attracted much attention for treating cancer in preclinical studies. Despite the anticancer capabilities of these phytochemical compounds, systemic toxicity, medication resistance, and limited absorption re

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… Through a series of enzymatic steps, there is the formation of indole glycerol phosphate takes place. Both α and ß subunits of the tryptophan synthase enzyme participate in the formation of tryptophan. … Tasumatrol B showed significant cytotoxicity compared to other compounds | Qayum et al. (2019) Binding energy range: 6.9 kcal/mol to -7.1 kcal/mol 2 | Chemical Synthesis by click chemistry | Topoisomerase | Podophyllotoxin-glycerol triazoles | MTT assay was performed using Du145, A-549, MCF-7 and HeLa …

How to Treat Melanoma? The Current Status of Innovative Nanotechnological Strategies and the Role of Minimally Invasive Approaches like PTT and PDT.

Melanoma is the most aggressive type of skin cancer, the incidence and mortality of which are increasing worldwide. Its extensive degree of heterogeneity has limited its response to existing therapies. For many years the therapeutic strategies were limited to surgery, radiotherapy, and chemotherapy. Fortunately, advances in knowledge have allowed the development of new therapeutic strategies. Despite the undoubted progress, alternative therapies are still under research. In this context, nanotechnology is also positioned as a strong and promising tool to develop nanosystems that act as drug ca

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… Abbreviations: ClAlPc, aluminum chloride phthalocyanine; DHA-dFdC, docosahexaenoyl difluorodeoxycytidine; DMNs, dissolving microneedles; ECIS, electrical cell-substrate impedance sensing; GMS, glycerol monostearate; i.v., intravenous; MTT, dimethylthiazol diphenyl tetrazolium bromide; PDT, photodynamic … Abbreviations: CTX, cyclophosphamide; DLS, dynamic light scattering; DTIC, dacarbazine; DTX, docetaxel; GMS, glycerol monostearate; HPLC, high performance liquid chromatography; i.p., intraperitoneal; IPM, isopropyl myristate; i.v., intravenous; LEM2, carbaldehyde dimethoxyxanthone; MTT, dimethylthiazol …

Nostoc commune-derived scytonemin induced mitochondrial cell death in leukemia models.

Cyanobacteria have long attracted scientific interest through their potential application in the development of new therapeutic approaches, particularly those related to the treatment of cancer. In this study, the antiproliferative effects of Nostoc commune extract (NOS) and the cyanobacterial compound scytonemin (SCY) were evaluated against a variety of in vitro cancer models, including cervix, colon, breast, lung, and leukemia cell lines, using resazurin assays. Both of the studied compounds were found to have inhibited metabolic activity in a dose-dependent manner, with IC50 values ranging

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… A Laemli-Lysis buffer (composed of glycerol, 20% sodium dodecyl sulphate (SDS), 1 M Tris/HCl (pH = 8.6), deionized H 2 O, protease and phosphatase inhibitors; all components obtained from Merck, Darmstadt, Germany) was used to prepare cell lysates. …

Адаптация эукариот-подобных PRS к прокариот-подобным tRNAPro.

Синтеты Проли-ТРНА (ПРОРС) уникальны среди аминоачил-тРНК (ААРС) two различные структурные архитектуры различных организмов: прокариота-подобные (П-тип) и эукариоте/археон-подобные (Е-тип). Интересно, что Бакиллус Тюрингьенси гавань обоих типов, сосуществует P-тип (BtProRS1) и E-тип PRS (BtProRS2). Несмотря на свои различия, оба фермента формально выражаются и функционируют в vivo. По аналогии с BtProRS1, BtPRS2 выборочно заряжает TRNAPro типа P и демонстрирует более высокий допуск к галоугинону, чем каноническая PRS. Однако эти two Изозимы признают основные идентификационные элементы типа P t

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… As glycerol is the only carbon source in YPG, yeast needs functional mitochondria to metabolize this non-fermentable organic compound through oxidative phosphorylation. …

Identification of new candidate biomarkers to support doxorubicin treatments in canine cancer patients.

BackgroundBoth human and veterinary cancer chemotherapy are undergoing a paradigm shift from a "one size fits all" approach to more personalized, patient-oriented treatment strategies. Personalized chemotherapy is dependent on the identification and validation of biomarkers that can predict treatment outcome and/or risk of toxicity. Many cytotoxic chemotherapy agents, including doxorubicin, base their mechanism of action by interaction with DNA and disruption of normal cellular processes. We developed a high-resolution/accurate-mass liquid chromatography-mass spectrometry DNA screening approac

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… Briefly, 10 μL of bacterial stock culture in 25% glycerol were inoculated in 5 mL M9 minimal media starter culture and incubated overnight in a thermoshaker (37 °C, 200 rpm). …

Additive Pharmacological Interaction between Cisplatin (CDDP) and Histone Deacetylase Inhibitors (HDIs) in MDA-MB-231 Triple Negative Breast Cancer (TNBC) Cells with Altered Notch1 Activity-An Isobolographic Analysis.

The aim of this study was to investigate the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two histone deacetylase inhibitors (HDIs)-valproic acid (VPA) and vorinostat (SAHA) in the triple negative breast cancer (TNBC) cells. Stable breast cancer (BC) cell lines with increased and decreased activity of Notch1 were generated using a transfection method. The type of interaction between CDDP and the HDIs was determined by isobolographic analysis of cell proliferation in MDA-MB-231 cells with differential levels of Notch1 activity in vitro.

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… For Western blot analysis, supernatants of RIPA cell lysates were solubilized in 6 x Laemmli Sample Buffer (50% glycerol, 10% SDS, 300 mM Tris-HCl pH 6.8, 0.05% bromophenol blue, 6.25% β-mercaptoethanol) and denaturated for 5 min at 100 °C. 20 µg of protein extracts were loaded on 10% SDS polyacrylamide …

FGFR3, HRAS, KRAS, NRAS and PIK3CA mutations in bladder cancer and their potential as biomarkers for surveillance and therapy.

BackgroundFifty percent of patients with muscle-invasive bladder cancer (MI-BC) die from their disease and current chemotherapy treatment only marginally increases survival. Novel therapies targeting receptor tyrosine kinases or activated oncogenes may improve outcome. Hence, it is necessary to stratify patients based on mutations in relevant oncogenes. Patients with non-muscle-invasive bladder cancer (NMI-BC) have excellent survival, however two-thirds develop recurrences. Tumor specific mutations can be used to detect recurrences in urine assays, presenting a more patient-friendly diagnostic

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… Each multiplex PCR reaction was performed in a total volume of 15 µl containing 0.17 mM dNTPs (Roche, Basel, Switzerland), 1.5 mM MgCl2, 5% glycerol (Fluka, Buchs SG, Switzerland), 0.3–1.2 µM of the appropriate primer combination (Invitrogen, Carlsbad, CA), 1× PCR buffer, and 0.5 units of Go Taq DNA …

Протекционный субъект PSMD1 является ключевой терапевтической целью в множестве миеломы.

Мы пришли к выводу, что PSMD1 - ключевой субъект протеиновой регуляционной частицы 19S - был чрезмерно экспрессирован и коррелировал с плохим прогнозом в множестве миеломы (ММ). Генетическое истощение PSMD1 снизило жизнеспособность раковых клеток, вызвало поликутилизированное накопление белка и способствовало апоптозу. Протеомический анализ показал активацию иммунных путей, что свидетельствует о потенциале иммунной модуляции. Нацеливание PSMD1 на незначительную поражающую РНК (SIRNA), доставляемую через липидные наночастицы (LNPs), уменьшило рост опухоли в линиях клеток MM и первичных проб пац

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… enrichment analysis (GSEA) software, 31 , 32 focusing on the Human Molecular Signature Database hallmark gene sets. 33 Preparation of LNP The ionizable cationic lipid DLIn-MC3-DMA (MC3), cholesterol, DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine), and polyethylene glycol-DMG (1,2-dimyristoyl-rac-glycerol …

Assessment of the availability of repurposed orphan drugs in India.

India has a massive burden of rare diseases (RDs), with an estimated 96 million people living with RDs but limited options for treatment. Repurposing drugs used for other common conditions are essential alternative for RDs due to their cost-effectiveness and reduced timeline. India's patent regime prevents the evergreening of drugs, and a large generic manufacturing industry provides ample opportunity to explore the potential of repurposed drugs for treating RDs, known as repurposed orphan drugs (ROD). However, there is no portal or other source for information on orphan drugs in India. This s

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… Among these five drugs lomitapide; glycerol phenylbutyrate; tiopronin; calcium, magnesium, potassium, and sodium oxybates; cobicistat were mentioned in a CDSCO letter about having approval for manufacturing and packing in India [ 39 – 42 ] for export to EU, but they were not listed in CDSCO drug list …

Cannabidiol on the Path from the Lab to the Cancer Patient: Opportunities and Challenges.

Cannabidiol (CBD), a major non-psychotropic component of cannabis, is receiving growing attention as a potential anticancer agent. CBD suppresses the development of cancer in both in vitro (cancer cell culture) and in vivo (xenografts in immunodeficient mice) models. For critical evaluation of the advances of CBD on its path from laboratory research to practical application, in this review, we wish to call the attention of scientists and clinicians to the following issues: (a) the biological effects of CBD in cancer and healthy cells; (b) the anticancer effects of CBD in animal models and clin

Direct Endoplasmic Reticulum Targeting by the Selective Alkylphospholipid Analog and Antitumor Ether Lipid Edelfosine as a Therapeutic Approach in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, shows a dismal and grim overall prognosis and survival rate, which have remained virtually unchanged for over half a century. PDAC is the most lethal of all cancers, with the highest mortality-to-incidence ratio. PDAC responds poorly to current therapies and remains an incurable malignancy. Therefore, novel therapeutic targets and drugs are urgently needed for pancreatic cancer treatment. Selective induction of apoptosis in cancer cells is an appealing approach in cancer therapy. Apoptotic cell death is highly

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… Edelfosine was first synthesized in 1969 by Günter Kny [ 171 ], a chemical diploma student in Otto Westphal’s group, following the previous studies of Bernd Arnold and Hans Ulrich Weltzien synthesizing 1- O -alkyl- and 2- O -methyl derivatives of glycerol [ 146 ]. … The molecular structure of edelfosine is critical for its biological actions [ 146 , 147 , 172 ], and the presence of the ether bonds in C1 and C2 of the glycerol backbone—instead of the typical ester bonds in a phospholipid molecule—makes this ether lipid very metabolically stable in comparison with …

Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.

Autophagy is a highly conserved multistep process and functions as passage for degrading and recycling protein aggregates and defective organelles in eukaryotic cells. Based on the nature of these materials, their size and degradation rate, four types of autophagy have been described, i.e. chaperone mediated autophagy, microautophagy, macroautophagy, and selective autophagy. One of the major regulators of this process is mTOR, which inhibits the downstream pathway of autophagy following the activation of its complex 1 (mTORC1). Alkylphosphocholine (APC) derivatives represent a novel class of a

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… An ether linkage to its glycerol backbone characterizes the prototype of ALPs, edelfosine ( Kaleagasioglu et al., 2019 ; Zaremberg et al., 2019 ). … The first APC generation is represented by miltefosine (hexadecylphosphocholine, HPC), which lacks the glycerol backbone and thus shows a less complex metabolism ( Kaleagasioglu et al., 2019 ; Zaremberg et al., 2019 ). …