ABSTRACT
During tumorigenesis, cancer cells generate complex, unresolved interactions with the surrounding oxystressed cellular milieu called tumor microenvironment (TM) that favors spread of cancer to other body parts. This dissemination of cancer cells from the primary tumor site is the main clinical challenge in cancer treatment. In addition, the significance of enhanced oxidative stress in TM during cancer progression still remains elusive. Thus, the present study was performed to investigate the molecular and cytoskeletal alterations in breast cancer cells associated with oxystressed TM that potentiates metastasis. Our results showed that depending on the extent of oxidative stress in TM, cancer cells exhibited enhanced migration and survival with reduction of chemosensitivity. Corresponding ultrastructural analysis showed radical cytoskeletal modifications that reorganize cell-cell interactions fostering transition of epithelial cells to mesenchymal morphology (EMT) marking metastasis, which was reversed upon antioxidant treatment. Decreased E-cadherin and increased vimentin, Twist1/2 expression corroborated the initiation of EMT in oxystressed TM-influenced cells. Further evaluation of cellular energetics demonstrated significant metabolic reprogramming with inclination towards glucose or external glutamine from TM as energy source depending on the breast cancer cell type. These observations prove the elemental role of oxystressed TM in cancer progression, initiating EMT and metabolic reprogramming. Further cell-type specific metabolomic analysis would unravel the alternate mechanisms in cancer progression for effective therapeutic intervention. Graphical abstract Schematic representation of the study and proposed mechanism of oxystressed TM influenced cancer progression. Cancer cells exhibit a close association with tumor microenvironment (TM), and oxystressed TM enhances cancer cell migration and survival and reduces chemosensitivity. Oxystressed TM induces dynamic cytomorphological variations, alterations in expression patterns of adhesion markers, redox homeostasis, and metabolic reprogramming that supports epithelial to mesenchymal transition and cancer progression.
Subject(s)
Energy Metabolism , Epithelial-Mesenchymal Transition , Neoplasms/metabolism , Neoplasms/pathology , Oxidative Stress , Tumor Microenvironment , Animals , Antioxidants/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Drug Resistance, Neoplasm , Humans , Hydrogen Peroxide/metabolism , Hydrogen Peroxide/pharmacology , Lactate Dehydrogenases/metabolism , Metabolomics/methods , Mice , Models, Biological , Neoplasms/enzymology , Oxidative Stress/drug effects , Proton Magnetic Resonance Spectroscopy , Reactive Oxygen Species/metabolism , Tumor Microenvironment/drug effectsABSTRACT
OBJECTIVE: The purpose of the present study was to evaluate the nephroprotective and antioxidant properties of Triphala against bromobenzene-induced nephrotoxicity in female Wistar albino rats. METHODS: Animals were divided into five groups of six rats and treated as follows: Group I was a normal control and received no treatment, Group II received only bromobenzene (10 mmol/kg), Groups III and IV received bromobenzene and Triphala (250 and 500 mg/kg, respectively), Group V received Triphala alone (500 mg/kg), and Group VI received bromobenzene and silymarin (100 mg/kg). Antioxidant status and serum kidney functional markers were analyzed. RESULTS: Bromobenzene treatment resulted in significant (P< 0.05) decreases in the activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase as well as total reduced glutathione. There was a significant (P< 0.05) increase in lipid peroxidation in kidney tissue homogenates. There were significant (P< 0.05) reductions in the levels of serum total protein and albumin as well as significant (P< 0.05) increases in serum creatinine, urea and uric acid. The oral administration of two different doses (250 and 500 mg/kg) of Triphala in bromobenzene-treated rats normalized the tested parameters. The histopathological examinations of kidney sections of the experimental rats support the biochemical observations. CONCLUSION: Triphala treatment alleviated the nephrotoxic effects of bromobenzene by increasing the activities of antioxidant enzymes and reducing the levels of lipid peroxidation and kidney functional markers.
Subject(s)
Acute Kidney Injury/prevention & control , Kidney , Phyllanthus emblica , Plant Preparations , Terminalia , Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnosis , Acute Kidney Injury/metabolism , Animals , Antioxidants/pharmacology , Bromobenzenes/pharmacology , Disease Models, Animal , Female , Kidney/metabolism , Kidney/pathology , Kidney Function Tests , Medicine, Ayurvedic , Plant Preparations/chemistry , Plant Preparations/pharmacology , Plant Structures , Protective Agents/pharmacology , Rats , Rats, Wistar , Silymarin/pharmacology , Treatment OutcomeABSTRACT
The purpose of the present study was to evaluate the nephroprotective and antioxidant properties of Triphala against bromobenzene-induced nephrotoxicity in female Wistar albino rats.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy of boswellic acid against monosodium urate crystal-induced inflammation in mice.</p><p><b>METHODS</b>The mice were divided into four experimental groups. Group I served as control; mice in group II were injected with monosodium urate crystal; group III consisted of monosodium urate crystal-induced mice who were treated with boswellic acid (30 mg/kg/b.w.); group IV comprised monosodium urate crystal-induced mice who were treated with indomethacin (3 mg/kg/b.w.). Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF-α were determined in control and monosodium urate crystal-induced mice. In addition, the levels of β-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes (PMNL) in vitro.</p><p><b>RESULTS</b>The activities of lysosomal enzymes, lipid peroxidation, and tumour necrosis factor-α levels and paw volume were increased significantly in monosodium urate crystal-induced mice, whereas the activities of antioxidant status were in turn decreased. However, these changes were modulated to near normal levels upon boswellic acid administration. In vitro, boswellic acid reduced the level of β-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated PMNL in concentration dependent manner when compared with control cells.</p><p><b>CONCLUSIONS</b>The results obtained in this study further strengthen the anti-inflammatory/antiarthritic effect of boswellic acid, which was already well established by several investigators.</p>
