ABSTRACT
Aim: Nyctanthes arbortristis Linn is a potential anti-diabetic drug that reduces glucose levels by delaying carbohydrate digestion. The tumor microenvironment is characterized by elevated glucose levels that activate various genes, such as mTOR. mTOR plays a critical role in maintaining the hypoxic environment and inhibiting autophagy. Although natural compounds pose fewer side effects, their hydrophobic nature makes these compounds not suitable as therapeutics. Hence, we conjugated aqueous NAT into gold nanoparticles (AuNP) in the current study and evaluated the ability of the chosen drugs to induce cell death in breast cancer cells resistant to Paclitaxel. Materials and methods: Particle size analyzer, UV-Vis spectrophotometer, FTIR, and XRD were used in the present study to characterize NAT and Doxorubicin encapsulated AuNPs. To check the cytotoxic effect of AuNP-NAT and AuNP-doxorubicin on PacR/MCF-7 stem cells MTT assay was performed. RT-PCR was performed to check the altered expression of ferritinophagy-related genes. The proliferation and migration potential of the cells before and after treatment with the desired drug combinations was evaluated by clonogenic and scratch assays, respectively. Flow cytometry analysis was done to quantify apoptotic bodies and cell cycle arrest. Cellular ROS was determined using DCD-FA staining. Results and conclusion: NAT and doxorubicin loaded into AuNP showed enhanced stability and induced ferritinophagy in PacR/MCF-7 stem cells. The obtained results suggest that AuNP-NAT, combined with a low AuNP-Doxorubicin nanoconjugate dose, might be an effective anti-neoplastic drug targeting the necroptosis-autophagy axis, thereby reducing the adverse side-effects induced by the conventional chemotherapeutic drugs.
ABSTRACT
Cancer is a cellular impairment disorder characterized by the loss of cell cycle regulation leading to aberrant cell proliferation. Cell-cell communication plays a crucial role in cell signaling which is highly disrupted in various malignancies. Tight junctions (TJs) are major proteins that regulate the proper communication, and the dysregulation of TJ proteins makes these tumor cells more aggressive, leading to tumor invasion and metastasis. Hence targeting TJs might be a novel insight towards addressing these highly invasive, metastatic tumors. Due to the prohibitive costs of treatments, side effects, and development of resistance, herbal medications comprising bioactive ingredients have become more popular for various human ailments. Unfortunately, the importance of natural compounds has significantly reduced due to the development of modern synthetic techniques to formulate drugs. However, the pharmaceutical industry that adopts chemistry-based drug development in combination with high throughput synthesis have not resulted in the expected drug productivity. Hence, the focus was shifted back to natural compounds in search of novel drugs with advanced technology to isolate the biologically active compound from the natural ones. The current review delivers the importance of TJ regulation, promoting it through phytochemicals to target malignant tumor cells.
ABSTRACT
BACKGROUND: Alterations in the levels of nutrients like calcium, ferritin, and electrolytes play a pivotal role in human physiology and might serve as biomarkers. Ferritin, an iron storage protein is important in various metabolic reactions of both cancer and cancer stem cells (CSCs) and is found to regulate 'stemness' leading to cancer relapse. Interestingly, ferritin levels are found to be regulated by calcium uptake. Several studies have shown that high levels of calcium inhibit absorption of iron, thereby reducing ferritin levels. In the present study, we evaluated and correlated the serum ferritin and calcium levels in pre- and post-treated hormone-dependent female cancers and deciphered their role in tumor recurrence and relapse. MATERIALS AND METHODS: The present retrospective study was approved by the Institutional Ethical Committees (IEC) of GIMSR (No. GIMSR/Admn./Ethics/approval/IEC-3/2021), and Omega cancer hospitals (Reg No: ECR/1486/Inst/AP/2020). Serum from 197 clinical samples diagnosed with breast, cervical, and ovarian cancers (99 pre-and 98 post-treatment) and 10 blood samples were analyzed for ferritin and calcium using auto bioanalyzer and sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Ferritin levels were elevated in both pre- and post-treatment hormone-dependent female cancer patients while calcium levels showed gradual decrease. The mean ferritin value for pre-treatment was 0.0409 mg/dL while it was 0.0428 mg/dL for post-treatment hormone-dependent female cancer. CONCLUSION: Our results suggest that hypocalcaemia in post-treatment cancer patients leads to ferritin accumulation which might make these patients more prone to tumor recurrence and relapse.
ABSTRACT
Breast cancer is one of the most common malignancies in women and the leading cause of cancer mortality. Hypercholesterolemia and obesity are potential risk factors for the incidence of breast cancer, and their detection can enhance cancer prevention. In this paper, we discuss the current state of investigations on the importance of lipoproteins, such as low denisity lipoproteins (LDL) and high density lipoproteins (HDL), and cholesterol transporters in the progression of breast cancer, and the therapeutic strategies to reduce breast cancer mortality. Although some research has been unsuccessful at uncovering links between the roles of lipoproteins and breast cancer risk, major scientific trials have found a straight link between LDL levels and incidence of breast cancer, and an inverse link was found between HDL and breast cancer development. Cholesterol and its transporters were shown to have significant importance in the development of breast cancer in studies on breast cancer cell lines and experimental mice models. Instead of cholesterol, 27-hydroxycholesterol, which is a cholesterol metabolite, is thought to promote propagation and metastasis of estrogen receptor-positive breast cancer cell lines. Alteration of lipoproteins via oxidation and HDL glycation are thought to activate many pathways associated with inflammation, thereby promoting cellular proliferation and migration, leading to metastasis while suppressing apoptosis. Medications that lower cholesterol levels and apolipoprotein A-I mimics have appeared to be possible therapeutic agents for preventing excessive cholesterol's role in promoting the development of breast cancer.
ABSTRACT
Iron is a crucial element required for the proper functioning of the body. For instance, hemoglobin is the vital component in the blood that delivers oxygen to various parts of the body. The heme protein present in hemoglobin comprises iron in the form of a ferrous state which regulates oxygen delivery. Excess iron in the body is stored as ferritin and would be utilized under iron-deficient conditions. Surprisingly, cancer cells as well as cancer stem cells have elevated ferritin levels suggesting that iron plays a vital role in protecting these cells. However, apart from the cytoprotective role iron also has the potential to induce cell death via ferroptosis which is a non-apoptotic cell death dependent on iron reserves. Apoptosis a caspase-dependent cell death mechanism is effective on cancer cells however little is known about its impact on cancer stem cell death. This paper focuses on the molecular characteristics of apoptosis and ferroptosis and the importance of switching to ferroptosis to target cancer stem cells death thereby preventing cancer relapse. To the best of our knowledge, this is the first review to demonstrate the importance of intracellular iron in regulating the switching of tumor cells and therapy resistant CSCs from apoptosis to ferroptosis.
